ProfessorStephenDurham

Turner PJ, Ansotegui IJ, Campbell DE, Cardona V, Carr S, Custovic A, Durham S, Ebisawa M, Geller M, Gonzalez-Estrada A, Greenberger PA, Hossny E, Irani C, Leung ASY, Levin ME, Muraro A, Oppenheimer JJ, Ortega Martell JA, Pouessel G, Rial MJ, Senna G, Tanno LK, Wallace DV, Worm M, Morais-Almeida M, WAO Anaphylaxis Committee and WAO Allergen Immunotherapy Committeeet al., 2024, Updated grading system for systemic allergic reactions: Joint Statement of the World Allergy Organization Anaphylaxis Committee and Allergen Immunotherapy Committee, The World Allergy Organization Journal, Vol: 17, ISSN: 1939-4551

There is a lack of consensus over the description and severity assignment of allergic adverse reactions to immunotherapy, although there seems to be a consensus at least in terms of using the World Allergy Organization (WAO) grading systems to describe local adverse events for Sublingual Immunotherapy (SLIT) and Systemic Allergic Reactions (SARs) to Subcutaneous Immunotherapy (SCIT) amongst the major national/regional allergy societies. In this manuscript, we propose a modification of the previous WAO Grading system for SARs, which aligns with the newly-proposed Consortium for Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions in Food Allergy (version 3.0). We hope this can facilitate a unified grading system appropriate to SARs due to allergen immunotherapy, independent of allergen and route of administration, and across clinical and research practice.

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Blaiss MS, Durham SR, Bernstein D, Stranzl T, Lindholm M, Nolte H, Andersen KF, Roberts Get al., 2024, Sublingual Tablet Immunotherapy Improves Quality of Life in Adults With Allergic Rhinoconjunctivitis., J Allergy Clin Immunol Pract

BACKGROUND: Allergic rhinitis with or without conjunctivitis can negatively impact many aspects of quality of life (QoL). The efficacy and safety of standardized quality (SQ) sublingual immunotherapy (SLIT) tablets have been confirmed across large clinical trials in adults with grass, tree, ragweed, and house dust mite (HDM) allergic rhinitis with or without conjunctivitis. OBJECTIVE: This pooled analysis investigates whether the reduction in symptom burden found across the clinical trials is supported by improvements in QoL. METHODS: A total of 11 phase II/III randomized placebo-controlled trials across the SQ grass, tree, ragweed, and HDM SLIT tablets (grass: N = 3179; ragweed: N = 767; tree: N = 634; HDM: N = 2221) were included. QoL was assessed using the standardized Rhinitis Quality of Life Questionnaire (RQLQ), with the exception of 3 grass trials, which used the nonstandardized version. The overall RQLQ scores were expressed as a mean of 7 domains. In the pooled analysis, treatment was used as fixed effect; and the trial, and the interaction between region/country and trial as random effects. RESULTS: The pooled analysis showed consistent and statistically significant improvements in overall RQLQ scores across all 4 SQ SLIT tablets versus placebo (pooled estimate [95% CI], P value-grass: -0.20 [-0.28 to -0.12], P < .001; tree: -0.42 [-0.58 to -0.26], P < .001; ragweed: -0.36 [-0.55 to -0.17], P < .001; HDM: -0.28 [-0.39 to -0.17], P < .001). Furthermore, significant improvements versus placebo for all 4 SQ SLIT tablets were seen across the 7 individual domains. CONCLUSIONS: The proven efficacy of SQ SLIT tablets to reduce symptoms across 4 of the most common respiratory allergens is supported by concurrent significant improvements in RQLQ scores overall and for all 7 domains.

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Arshad H, Lack G, Durham SR, Penagos M, Larenas-Linnemann D, Halken Set al., 2024, Prevention Is Better than Cure: Impact of Allergen Immunotherapy on the Progression of Airway Disease., J Allergy Clin Immunol Pract, Vol: 12, Pages: 45-56

Allergen immunotherapy is highly effective for seasonal pollinosis. Three years of treatment results in long-term efficacy. This disease modification is accompanied by downregulation of allergen-specific Th2 responses and the induction of persistent specific IgG- and IgA-associated IgE-blocking activity. In children with seasonal rhinitis, both subcutaneous and sublingual pollen immunotherapy have been shown to reduce the development of asthma symptoms and asthma medication requirements. House dust mite tablet allergen immunotherapy has been shown to be effective for perennial mite-driven rhinitis in adults and children and may suppress asthma exacerbations, whereas its long-term efficacy has yet to be explored. The success of primary prevention of peanut allergy in childhood by introduction of peanut into the diet during infancy provides a strong rationale to explore whether primary prevention of inhalant allergies and asthma may also be possible. House dust mite allergy is a major risk factor for developing asthma. Preliminary data in at-risk children suggest that sublingual house dust mite immunotherapy initiated during infancy could reduce the onset of multiple allergen sensitizations and prevent the development of asthma at age 6 years. This possibility should now be explored in an adequately powered, prospectively randomized controlled trial.

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Fokkens W, Trigg A, Lee SE, Chan RH, Diamant Z, Hopkins C, Howarth P, Lund V, Mayer B, Sousa AR, Yancey S, Tabberer M, Ardusso L, Bergna M, De Salvo M, Elías P, García G, Maspero J, Rojas R, Scherbovsky PS, Tolcachier A, Wehbe L, Yañez A, Bardin P, Barnes S, Gillman A, Harvey R, Sader C, Singh N, Del Carpio J, Corriveau MN, Desrosiers M, Janjua A, Kilty S, Sommer D, Sowerby L, Spafford P, Betz C, Beule A, Chaker A, Cuevas M, Groeger M, Klimek L, Olze H, van Schaik C, Wagenmann M, Wollenberg B, Yarin Y, Cho HJ, Dhong HJ, Kim CH, Kim S, Rhee CS, Kim SW, Kim HY, Fokkens WJ, Bronescu V, Mella C, Neagos A, Radeanu D, Stefan C, Edin A, Karpischenko S, Khanova F, Mirzabekyan E, Ovchinnikov A, Polyakov D, Ryazantsev S, Svistushkin V, Tarasova G, Yakusevich V, Emanuelsson CA, Hellgren J, Jangard M, Mårtensson A, Toll K, Carrie S, Durham S, Gane S, Hobson J, Kara N, Leong S, Massey N, Scaddin G, Armstrong M, Blotter J, Brown M, Courville T, Damask C, DeConde A, Ehmer D, Fatakia A, Franzese C, Han J, Higgins T, Kerwin E, LaForce C, Lee S, Marple B, Matz Jet al., 2023, Mepolizumab improvements in health-related quality of life and disease symptoms in a patient population with very severe chronic rhinosinusitis with nasal polyps: psychometric and efficacy analyses from the SYNAPSE study, Journal of Patient-Reported Outcomes, Vol: 7

Background: Although the psychometric properties of patient-reported outcome measures (e.g. the 22-item Sino-nasal Outcomes Test [SNOT-22]) in chronic rhinosinusitis with nasal polyps (CRSwNP) have been defined, these definitions have not been extensively studied in patients with very severe CRSwNP, as defined by recurrent disease despite ≥ 1 previous surgery and a current need for further surgery. Therefore, the psychometric properties of the symptoms visual analogue scales (VAS) were evaluated, and meaningful within-patient change thresholds were calculated for VAS and SNOT-22. Methods: SYNAPSE (NCT03085797), a randomized, double-blind, placebo-controlled, 52-week trial, assessed the efficacy and safety of 4-weekly mepolizumab 100 mg subcutaneously added to standard of care in very severe CRSwNP. Enrolled patients (n = 407) completed symptom VAS (six items) daily and SNOT-22 every 4 weeks from baseline until Week 52. Blinded psychometric assessment of individual and composite VAS was performed post hoc, including anchor-based thresholds for meaningful within-patient changes for VAS and SNOT-22, supported by cumulative distribution function and probability density function plots. The effect of mepolizumab versus placebo for 52 weeks on VAS and SNOT-22 scores was then determined using these thresholds using unblinded data. Results: Internal consistency was acceptable for VAS and SNOT-22 scores (Cronbach’s α-coefficients ≥ 0.70). Test–retest reliability was demonstrated for all symptom VAS (Intra-Class Correlation coefficients > 0.75). Construct validity was acceptable between individual and composite VAS and SNOT-22 total score (r = 0.461–0.598) and between individual symptom VAS and corresponding SNOT-22 items (r = 0.560–0.780), based upon pre-specified ranges. Known-groups validity assessment demonstrated generally acceptable validity based on factors associated with respiratory health, with all VAS responsive

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Meng X, Layhadi JA, Keane ST, Cartwright NJK, Durham SR, Shamji MHet al., 2023, Immunological mechanisms of tolerance: central, peripheral and the role of T and B cells, Asia Pacific Allergy, Vol: 13, Pages: 175-186, ISSN: 2233-8268

T and B cells are key components of the adaptive immune system. Through their immune properties and their interactions with other immune cells and cytokines around them, they build a complex network to achieve immune tolerance and maintain homeostasis of the body. This is achieved through mechanisms of central and peripheral tolerance, both of which are associated with advantages and disadvantages. For this reason, the immune system is tightly regulated and their dysregulation can result in the subsequent initiation of various diseases. In this review, we will summarize the roles played by T cells and B cells within immune tolerance with specific examples in the context of different diseases that include allergic disease. In addition, we will also provide an overview on their suitability as biomarkers of allergen-specific immunotherapy.

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Ewan PW, Durham SR, Scadding GK, Holgate STet al., 2023, Celebrating 75 years of BSACI., Clin Exp Allergy, Vol: 53, Pages: 1236-1238

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Altman MC, Segnitz RM, Larson D, Jayavelu ND, Smith M, Patel S, Scadding GW, Qin T, Sanda S, Steveling E, Eifan AO, Penagos M, Jacobson MR, Parkin RV, Shamji MH, Togias A, Durham SRet al., 2023, Nasal and blood transcriptomic pathways underpinning the clinical response to grass pollen immunotherapy, Journal of Allergy and Clinical Immunology, Vol: 152, Pages: 1247-1260, ISSN: 0091-6749

BACKGROUND: Allergen immunotherapy (AIT) is a well-established disease-modifying therapy for allergic rhinitis, yet the fundamental mechanisms underlying its clinical effect remain inadequately understood. OBJECTIVE: The GRASS study was a randomized, double-blind, placebo-controlled trial of timothy grass allergic individuals who received 2 years of placebo (n=30), subcutaneous (SCIT) (n=27), or sublingual immunotherapy (SLIT) (n=27) and were then followed for 1 additional year. Here we used yearly biospecimens from the GRASS study to identify molecular mechanisms of response. METHODS: We utilized longitudinal transcriptomic profiling of nasal brush and peripheral blood mononuclear cell (PBMC) samples after allergen provocation to uncover airway and systemic expression pathways mediating responsiveness to AIT. RESULTS: SCIT and SLIT demonstrated similar changes in gene module expression over time. In nasal samples, alterations included downregulation of pathways of mucus hypersecretion, leukocyte migration/activation, and endoplasmic reticulum stress (log2 fold changes (logFC) -0.133 to -0.640, FDRs <0.05). Interestingly, we observed upregulation of modules related to epithelial development, junction formation, and lipid metabolism (logFC 0.104 to 0.393, FDRs <0.05). In PBMCs, modules related to cellular stress response and type 2 cytokine signaling were reduced by immunotherapy (logFC -0.611 to -0.828, FDRs <0.05). Expression of these modules was also significantly associated with both Total Nasal Symptom Score and Peak Nasal Inspiratory Flow responses, indicating important links among treatment, module expression, and allergen response. CONCLUSION: Our results identify specific molecular responses of the nasal airway impacting barrier function, leukocyte migration activation, and mucus secretion, that are affected by both SCIT and SLIT, offering potential targets to guide novel strategies for AIT.

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Jutel M, Agache I, Zemelka-Wiacek M, Akdis M, Chivato T, del Giacco S, Gajdanowicz P, Gracia IE, Klimek L, Lauerma A, Ollert M, O'Mahony L, Schwarze J, Shamji MH, Skypala I, Palomares O, Pfaar O, Torres MJ, Bernstein JA, Cruz AA, Durham SR, Galli SJ, Gomez RM, Guttman-Yassky E, Haahtela T, Holgate ST, Izuhara K, Kabashima K, Larenas-Linnemann DE, von Mutius E, Nadeau KC, Pawankar R, Platts-Mills TAE, Sicherer SH, Park H-S, Vieths S, Wong G, Zhang L, Bilo MB, Akdis CAet al., 2023, Nomenclature of allergic diseases and hypersensitivity reactions: Adapted to modern needs: An EAACI position paper, ALLERGY, ISSN: 0105-4538

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Kappen J, Diamant Z, Agache I, Bonini M, Bousquet J, Canonica GW, Durham SRR, Guibas GVV, Hamelmann E, Jutel M, Papadopoulos NGG, Roberts G, Shamji MHH, Zieglmayer P, van Wijk RG, Pfaar Oet al., 2023, Standardization of clinical outcomes used in allergen immunotherapy in allergic asthma: An EAACI position paper, ALLERGY, ISSN: 0105-4538

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Spriggs K, Pfaar O, Pawankar R, Durham Set al., 2023, Is "Maintenance" a Misnomer? A Narrative Framework Setting the Right Expectations of Allergen Immunotherapy, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, Vol: 11, Pages: 2051-2053, ISSN: 2213-2198

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Bousquet J, Melén E, Haahtela T, Koppelman GH, Togias A, Valenta R, Akdis CA, Czarlewski W, Rothenberg M, Valiulis A, Wickman M, Akdis M, Aguilar D, Bedbrook A, Bindslev-Jensen C, Bosnic-Anticevich S, Boulet LP, Brightling CE, Brussino L, Burte E, Bustamante M, Canonica GW, Cecchi L, Celedon JC, Chaves Loureiro C, Costa E, Cruz AA, Erhola M, Gemicioglu B, Fokkens WJ, Garcia-Aymerich J, Guerra S, Heinrich J, Ivancevich JC, Keil T, Klimek L, Kuna P, Kupczyk M, Kvedariene V, Larenas-Linnemann DE, Lemonnier N, Lodrup Carlsen KC, Louis R, Makela M, Makris M, Maurer M, Momas I, Morais-Almeida M, Mullol J, Naclerio RN, Nadeau K, Nadif R, Niedoszytko M, Okamoto Y, Ollert M, Papadopoulos NG, Passalacqua G, Patella V, Pawankar R, Pham-Thi N, Pfaar O, Regateiro FS, Ring J, Rouadi PW, Samolinski B, Sastre J, Savouré M, Scichilone N, Shamji MH, Sheikh A, Siroux V, Sousa-Pinto B, Standl M, Sunyer J, Taborda-Barata L, Toppila-Salmi S, Torres MJ, Tsiligianni I, Valovirta E, Vandenplas O, Ventura MT, Weiss S, Yorgancioglu A, Zhang L, Abdul Latiff AH, Aberer W, Agache I, Al-Ahmad M, Alobid I, Ansotegui IJ, Arshad SH, Asayag E, Barbara C, Baharudin A, Battur L, Bennoor KS, Berghea EC, Bergmann KC, Bernstein D, Bewick M, Blain H, Bonini M, Braido F, Buhl R, Bumbacea RS, Bush A, Calderon M, Calvo-Gil M, Camargos P, Caraballo L, Cardona V, Carr W, Carreiro-Martins P, Casale T, Cepeda Sarabia AM, Chandrasekharan R, Charpin D, Chen YZ, Cherrez-Ojeda I, Chivato T, Chkhartishvili E, Christoff G, Chu DK, Cingi C, Correia de Sousa J, Corrigan C, Custovic A, D'Amato G, Del Giacco S, De Blay F, Devillier P, Didier A, do Ceu Teixeira M, Dokic D, Douagui H, Doulaptsi M, Durham S, Dykewicz M, Eiwegger T, El-Sayed ZA, Emuzyte R, Fiocchi A, Fyhrquist N, Gomez RM, Gotua M, Guzman MA, Hagemann J, Hamamah S, Halken S, Halpin DMG, Hofmann M, Hossny E, Hrubiško M, Irani C, Ispayeva Z, Jares E, Jartti T, Jassem E, Julge K, Just J, Jutel M, Kaidashev I, Kalayci O, Kalyoncu AF, Kardas P, Kirenga B, Kraxner Het al., 2023, Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis, Allergy, Vol: 78, Pages: 1169-1203, ISSN: 0105-4538

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.

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Durham SR, Shamji MH, 2023, Allergen immunotherapy: past, present and future, NATURE REVIEWS IMMUNOLOGY, Vol: 23, Pages: 317-328, ISSN: 1474-1733

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• Citations: 30

Dramburg S, Lau S, Matricardi P, Worm M, Akdis CA, Bachert C, Bochner B, Durham S, Ring J, Breiteneder H, Valenta R, Traidl-Hoffman Cet al., 2023, Obituary: Jorg Kleine-Tebbe, ALLERGY, Vol: 78, Pages: 1124-1125, ISSN: 0105-4538

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Layhadi J, Moya R, Tan TJ, Lenormand M, Sharif H, Parkin R, Vila-Nadal G, Fedina O, Zhu R, Laisuan W, Durham S, Carnés J, Shamji Met al., 2023, Single-cell RNA-Seq identifies precise tolerogenic cellular and molecular pathways induced by depigmented-polymerized grass pollen allergen extract, Journal of Allergy and Clinical Immunology, Vol: 151, Pages: 1357-1370.e9, ISSN: 0091-6749

Background:Immunological mechanism of action of allergoids remains poorly understood. Previous models of allergenicity and immunogenicity have yielded sub-optimal knowledge of these immunotherapeutic vaccine products. Novel single-cell RNA-seq technology offers a bridge to this gap in knowledge.Objective:To identify the underpinning tolerogenic molecular and cellular mechanisms of depigmented-polymerized Phleum pratense extract.MethodsThe molecular mechanisms underlying native Phleum pratense (Phl p), depigmented Phl p (DPG-Phl p), and depigmented-polymerized (DPG-POL-Phl p) allergoid were investigated using scRNA-seq. Allergen-specific Th2A, Tfh and IL-10+ Breg cells were quantified by flow cytometry in PBMCs from 16 grass pollen allergics (GPA) and 8 non-atopic controls (NAC). The ability of Phl p, DPG-Phl p and DPG-POL-Phl p to elicit FcεRI and FcεRII-mediated IgE responses was measured by basophil activation test and IgE-FAB assay.Results:ScRNA-seq analysis revealed that DPG-POL-Phl p downregulated genes associated with Th2 signaling, induced functional Tregs exhibiting immunosuppressive roles through CD52 and Siglec-10, modulated genes encoding immunoproteasome that dysregulate the processing and presentation of antigens to T cells and promoted a shift from IgE towards an IgA1 and IgG responses. In GPA, DPG-POL-Phl p exhibited reduced capacity to elicit proliferation of Th2A, IL-4+ Tfh and IL-21+ Tfh cells whilst being the most prominent at inducing CD19+CD5hiIL-10+ and CD19+CD5hiCD38intCD24intIL-10+ Breg cell subsets compared to Phl p (all, P<.05). Furthermore, DPG-POL-Phl p demonstrated a hypoallergenic profile through basophil activation and histamine release compared to Phl p (31.54-fold, P<.001).Conclusions:ScRNA-seq provides an in-depth resolution of the mechanisms underlying the tolerogenic profile of DPG-POL-Phl p.

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Varga EM, Durham SR, 2023, Allergen Injection Immunotherapy, Inflammatory Mechanisms in Allergic Diseases, Pages: 533-549, ISBN: 9780824705404

This chapter focuses on the use of allergen injection immunotherapy for the treatment of allergy to aeroallergens and insect stings. Allergen injection immunotherapy involves subcutaneous administration of increasing doses of allergen extract to improve symptoms and requirements for medication after natural reexposure to this allergen. Allergen injection immunotherapy has been highly effective in selected patients with clear evidence of IgE-mediated diseases. Allergen injection immunotherapy profoundly influences every step of this inflammatory process. Depending on the up-dosing regimen being used, clinical efficacy of allergen injection immunotherapy becomes evident within months and is maintained during continuation of treatment. Despite that numerous studies have unanimously stated the clinical efficacy of allergen immunotherapy, the mechanisms by which it exerts its beneficial effects are still not fully understood.

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Kasemsuk N, Ngaotepprutaram P, Kanjanawasee D, Suwanwech T, Durham SR, Canonica GW, Tantilipikorn Pet al., 2022, Local nasal immunotherapy for allergic rhinitis: A systematic review and meta-analysis, INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY, Vol: 12, Pages: 1503-1516, ISSN: 2042-6976

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• Citations: 3

Sousa-Pinto B, Anto A, Berger M, Dramburg S, Pfaar O, Klimek L, Jutel M, Czarlewski W, Bedbrook A, Valiulis A, Agache I, Amaral R, Ansotegui IJ, Bastl K, Berger U, Bergmann KC, Bosnic-Anticevich S, Braido F, Brussino L, Cardona V, Casale T, Canonica GW, Cecchi L, Charpin D, Chivato T, Chu DK, Cingi C, Costa EM, Cruz AA, Devillier P, Durham SR, Ebisawa M, Fiocchi A, Fokkens WJ, Gemicioglu B, Gotua M, Guzman M-A, Haahtela T, Carlos Ivancevich J, Kuna P, Kaidashev I, Khaitov M, Kvedariene V, Larenas-Linnemann DE, Lipworth B, Laune D, Matricardi PM, Morais-Almeida M, Mullol J, Naclerio R, Neffen H, Nekam K, Niedoszytko M, Okamoto Y, Papadopoulos NG, Park H-S, Passalacqua G, Patella V, Pelosi S, Nhan P-T, Popov TA, Regateiro FS, Reitsma S, Rodriguez-Gonzales M, Rosario N, Rouadi PW, Samolinski B, Sa-Sousa A, Sastre J, Sheikh A, Ulrik CS, Taborda-Barata L, Todo-Bom A, Tomazic PV, Toppila-Salmi S, Tripodi S, Tsiligianni I, Valovirta E, Ventura MT, Valero AA, Vieira RJ, Wallace D, Waserman S, Williams S, Yorgancioglu A, Zhang L, Zidarn M, Zuberbier J, Olze H, Anto JM, Zuberbier T, Fonseca JA, Bousquet Jet al., 2022, Real-world data using mHealth apps in rhinitis, rhinosinusitis and their multimorbidities, CLINICAL AND TRANSLATIONAL ALLERGY, Vol: 12

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• Citations: 5

Poto R, Shamji M, Marone G, Durham SR, Scadding GW, Varricchi Get al., 2022, Neutrophil Extracellular Traps in Asthma: Friends or Foes?, CELLS, Vol: 11

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• Citations: 1

Dua S, Ruiz-Garcia M, Bond S, Dowey J, Durham SR, Kimber I, Mills C, Roberts G, Skypala I, Wason J, Ewan P, Boyle RJ, Clark Aet al., 2022, Effects of Exercise and Sleep Deprivation on Reaction Severity During Oral Peanut Challenge: A Randomized Controlled Trial, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, Vol: 10, Pages: 2404-+, ISSN: 2213-2198

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• Citations: 6

Stoenchev K, Scadding G, Durham S, 2022, Case report: Immediate hypersensitivity to chloroxylenol and chlorocresol, Publisher: WILEY, Pages: 1011-1012, ISSN: 0954-7894

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Garcia HR, Wheeler K, Gunawardana N, Nadal GV, Scadding G, Durham S, Skypala Iet al., 2022, Optimal tests for predicting the outcome of oral food challenges to hazelnut, walnut and cashew in clinical practice, Publisher: WILEY, Pages: 1006-1006, ISSN: 0954-7894

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Penagos M, Durham SR, 2022, Long-term efficacy of the sublingual and subcutaneous routes in allergen immunotherapy, ALLERGY AND ASTHMA PROCEEDINGS, Vol: 43, Pages: 292-298, ISSN: 1088-5412

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• Citations: 8

Sousa-Pinto B, Azevedo LF, Jutel M, Agache I, Canonica GW, Czarlewski W, Papadopoulos NG, Bergmann K-C, Devillier P, Laune D, Klimek L, Anto A, Anto JM, Eklund P, Almeida R, Bedbrook A, Bosnic-Anticevich S, Brough HA, Brussino L, Cardona V, Casale T, Cecchi L, Charpin D, Chivato T, Costa EM, Cruz AA, Dramburg S, Durham SR, De Feo G, van Wijk RG, Fokkens WJ, Gemicioglu B, Haahtela T, Illario M, Carlos Ivancevich J, Kvedariene V, Kuna P, Larenas-Linnemann DE, Makris M, Mathieu-Dupas E, Melen E, Morais-Almeida M, Moesges R, Mullol J, Nadeau KC, Nhan P-T, O'Hehir R, Regateiro FS, Reitsma S, Samolinski B, Sheikh A, Stellato C, Todo-Bom A, Tomazic PV, Toppila-Salmi S, Valero A, Valiulis A, Ventura MT, Wallace D, Waserman S, Yorgancioglu A, Vries G, Eerd M, Zieglmayer P, Zuberbier T, Pfaar O, Fonseca JA, Bousquet Jet al., 2022, Development and validation of combined symptom-medication scores for allergic rhinitis*, ALLERGY, Vol: 77, Pages: 2147-2162, ISSN: 0105-4538

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• Citations: 23

Pfaar O, Bousquet J, Durham SR, Kleine-Tebbe J, Larche M, Roberts G, Shamji MH, van Wijk RGet al., 2022, One hundred and ten years of Allergen Immunotherapy: A journey from empiric observation to evidence, ALLERGY, Vol: 77, Pages: 454-468, ISSN: 0105-4538

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• Citations: 22

Palmer E, Layhadi J, Fedina O, Kappen J, Durham S, Shamji Met al., 2022, IL-10+regulatory B cells are dysregulated in patients with seasonal and perennial allergy, Publisher: MOSBY-ELSEVIER, Pages: AB95-AB95, ISSN: 0091-6749

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Layhadi J, Lenormand M, Kirtland M, Vila-Nadal G, Fedina O, Durham S, Tsitoura D, Shamji M, Wu Let al., 2022, Novel machine learning-led discovery of adjuvant drug candidate for allergen immunotherapy using synthetic toll-like receptor 2/6 agonist, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB71-AB71, ISSN: 0091-6749

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Turner P, Durham S, Skypala I, Boyle RBet al., 2022, No apparent impact of incremental dosing on eliciting dose at double-blind, placebo-controlled peanut challenge, Allergy, Vol: 77, Pages: 667-670, ISSN: 0105-4538

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Penagos M, Durham SR, 2022, Allergen immunotherapy for long-term tolerance and prevention, Journal of Allergy and Clinical Immunology, Vol: 149, ISSN: 0091-6749

Allergen immunotherapy is effective for the treatment of allergic rhinitis, allergic asthma and Hymenoptera venom allergy. In view of potential side effects, cost, and the necessary patient commitment, an important question is whether allergen immunotherapy provides persistent clinical benefits after treatment discontinuation. Here we appraise the existing evidence for long-term effects of both subcutaneous and sublingual immunotherapy in terms of clinical efficacy, immune mechanisms, prevention of asthma development and prevention of new allergen sensitisations. Evidence from large, randomised, double-blind, placebo-controlled clinical trials that include a follow-up phase after treatment cessation demonstrate long-term efficacy. The data strongly support recommendations in international guidelines that both sublingual and subcutaneous immunotherapy should be continued for a minimum of 3 years to achieve disease modification and long-term tolerance. Grass pollen immunotherapy for seasonal rhinitis may inhibit the onset of asthma symptoms and requirements for asthma medication. Whether early intervention in infancy with mite sublingual immunotherapy may prevent asthma remains to be tested.

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Cosme J, Durham SR, 2022, Allergen Immunotherapy for Allergic Diseases, Clinical Immunology: Principles and Practice, Sixth Edition, Pages: 1117-1126, ISBN: 9780702081668

Allergen immunotherapy is indicated in severe rhinoconjunctivitis with/without mild asthma. Immunotherapy, unlike anti-allergic drugs, has the potential to provide long-term clinical benefits for years after its discontinuation. Whereas subcutaneous immunotherapy has been the gold standard, the sublingual route has emerged as an effective and safer alternative for self-administration. In mite-allergic asthma, house dust mite sublingual tablets have been shown to prevent asthma exacerbations. Knowledge of mechanisms of immunotherapy has informed novel approaches and enabled the discovery of biomarkers to monitor response to treatment. Hymenoptera venom immunotherapy is highly effective and can be lifesaving. Oral immunotherapy directed against peanut and other foods have shown successful desensitization, but no long-term tolerance and a high level of side effects and is not for routine clinical use.

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Pfaar O, Bergmann K-C, Bonini S, Compalati E, Domis N, de Blay F, de Kam P-J, 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 AM, Sigsgaard T, Togias A, Willers C, Yang WH, Zieglmayer R, Zuberbier T, Zieglmayer Pet al., 2021, Technical standards in allergen exposure chambers worldwide - an EAACI Task Force Report., Allergy, Vol: 76, Pages: 3589-3612

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 III 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) airflow, 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.

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