Imperial College London

DrGuyScadding

Faculty of MedicineNational Heart & Lung Institute

Honorary Clinical Senior Lecturer
 
 
 
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g.scadding

 
 
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Royal BromptonRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
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114 results found

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.

Journal article

Hellings PW, Lau S, Scadding GK, Bjermer L, Backer V, Chaker AM, Conti DM, De Corso E, Diamant Z, Djukanovic R, Fokkens W, Gevaert P, Gray CL, Han JK, Heaney LG, Hoffmann HJ, Jesenak M, Johansen P, Kumaran MS, McDonald M, Melen E, Mullol J, Reitsma S, Ryan D, Scadding G, Schmid-Grendelmeier P, Teeling T, Odemyr M, Wahn Uet al., 2023, EUFOREA summit in Brussels 2023: <i>inspiring the future of allergy & respiratory care</i>, FRONTIERS IN ALLERGY, Vol: 4

Journal article

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

Journal article

Gauvreau GM, Davis BE, Scadding G, Boulet L-P, Bjermer L, Chaker A, Cockcroft DW, Dahlen B, Fokkens W, Hellings P, Lazarinis N, O'Byrne PM, Tufvesson E, Quirce S, Van Maaren M, de Jongh FH, Diamant Zet al., 2022, Allergen provocation tests in respiratory research: building on 50 years of experience, EUROPEAN RESPIRATORY JOURNAL, Vol: 60, ISSN: 0903-1936

Journal article

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

Conference paper

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

Conference paper

Scadding GK, Scadding GW, 2022, Biologics for chronic rhinosinusitis with nasal polyps (CRSwNP), JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 149, Pages: 895-897, ISSN: 0091-6749

Journal article

Scadding G, 2022, Real world evidence of long-term benefits from allergen-specific immunotherapy (AIT) Comment, LANCET REGIONAL HEALTH-EUROPE, Vol: 13, ISSN: 2666-7762

Journal article

Scadding GK, Scadding GW, 2022, Innate and adaptive immunity in allergic airway disease, CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 22, Pages: 10-15, ISSN: 1528-4050

Journal article

Verani L, Skypala IJ, Gunawardana N, Rey Garcia H, Scadding GWet al., 2021, Crustacean allergy in clinical practice: a retrospective study comparing diagnostic modalities, Publisher: WILEY, Pages: 1673-1673, ISSN: 0954-7894

Conference paper

Shamji MH, Larson D, Eifan A, Scadding GW, Qin T, Lawson K, Sever ML, Macfarlane E, Layhadi JA, Wurtzen PA, Parkin R, 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, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 148, Pages: 1061-+, ISSN: 0091-6749

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, Vol: 9, Pages: 1141-1153

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

Turner P, 2021, Identifying key priorities for research to protect the consumer with food hypersensitivity: a UK Food Standards Agency Priority Setting Exercise, Clinical and Experimental Allergy, Vol: 51, Pages: 1322-1330, ISSN: 0954-7894

IntroductionFood hypersensitivity (FHS), including food allergy, coeliac disease and food intolerance, is a major public health issue. The Food Standards Agency (FSA), an independent UK Government department working to protect public health and consumers’ wider interests in food, sought to identify research priorities in the area of FHS.MethodsA priority setting exercise was undertaken, using a methodology adapted from the James Lind Alliance—the first such exercise with respect to food hypersensitivity. A UK-wide public consultation was held to identify unanswered research questions. After excluding diagnostics, desensitization treatment and other questions which were out of scope for FSA or where FSA was already commissioning research, 15 indicative questions were identified and prioritized by a range of stakeholders, representing food businesses, patient groups, health care and academia, local authorities and the FSA.Results295 responses were received during the public consultation, which were categorized into 70 sub-questions and used to define 15 key evidence uncertainties (‘indicative questions’) for prioritization. Using the JLA prioritization framework, this resulted in 10 priority uncertainties in evidence, from which 16 research questions were developed. These could be summarized under the following 5 themes: communication of allergens both within the food supply chain and then to the end consumer (ensuring trust in allergen communication); the impact of socio-economic factors on consumers with FHS; drivers of severe reactions; mechanism(s) underlying loss of tolerance in FHS; and the risks posed by novel allergens/processing.DiscussionIn this first research prioritization exercise for food allergy and FHS, key priorities identified to protect the food-allergic public were strategies to help allergic consumers to make confident food choices, prevention of FHS and increasing understanding of socio-economic impacts. Diagnosis and trea

Journal article

Scadding GK, Scadding GW, 2021, Innate and Adaptive Immunity: ILC2 and Th2 Cells in Upper and Lower Airway Allergic Diseases, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, Vol: 9, Pages: 1851-1857, 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

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, VilĂ -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

Parkin R, Laisuan W, Sanver D, Scadding GW, Larson D, Durham SR, Shamji MHet al., 2020, Evaluating a method validation to deplete, purify and determine the function of IgG4, IgA1 and IgA2 antibodies induced following sublingual immunotherapy in patients with allergic rhinitis, European-Academy-of-Allergology-and-Clinical-Immunology Digital Congress (EAACI), Publisher: WILEY, Pages: 131-131, ISSN: 0105-4538

Conference paper

Sharif H, Fear D, Laisuan W, Zhang J, Yi Y, Parkin R, Fedina O, Nadal VG, Scadding G, Durham SR, Shamji MHet al., 2020, IL-10+T follicular helper cells (CXCR5+PD-1+CD4+TFH10) promote immune tolerance and regulate b cell function following allergen immunotherapy: A proof-of-concept cross-sectional study, European-Academy-of-Allergology-and-Clinical-Immunology Digital Congress (EAACI), Publisher: WILEY, Pages: 46-46, ISSN: 0105-4538

Conference paper

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

Hellings PW, Scadding G, Bachert C, Bjermer L, Canonica GW, Cardell LO, Carney AS, Constantinidis J, Deneyer L, Diamant Z, Durham S, Gevaert P, Harvey R, Hopkins C, Kjeldsen A, Klimek L, Lund VJ, Price D, Rimmer J, Ryan D, Roberts G, Sahlstrand-Johnson P, Salmi S, Samji M, Scadding G, Smith P, Steinsvik A, Wagenmann M, Seys S, Wahn U, Fokkens WJet al., 2020, EUFOREA treatment algorithm for allergic rhinitis, RHINOLOGY, Vol: 58, Pages: 618-622, ISSN: 0300-0729

Journal article

Marone G, Granata F, Pucino V, Pecoraro A, Heffler E, Loffredo S, Scadding GW, Varricchi Get al., 2019, The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma, FRONTIERS IN PHARMACOLOGY, Vol: 10

Journal article

Yi Y, Sharif H, Krasner-Macleod S, Parkin R, Scadding G, Durham S, Shamji Met al., 2019, Immunomodulation of CD4+CXCR5+PD-1+T follicular helper (Tfh) and CD4+CXCR5+PD-1+FoxP3+T follicular regulatory (Tfr) cell responses in grass pollen allergy, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 199-199, ISSN: 0105-4538

Conference paper

Sharif H, Acharya S, Dhondalay GK, Krasner-Macleod S, Parkin R, Scadding G, Durham S, Nadeau KC, Shamji Met al., 2019, Altered chromatin landscape in T follicular cells in seasonal allergic rhinitis and following allergen-specific immunotherapy, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 64-65, ISSN: 0105-4538

Conference paper

Garcia RH, Donovan J, Scadding G, Durham SR, Kelleher WP, Skypala IJet al., 2019, Is Pru p 3 a relevant test for lipid transfer protein allergy in a Northern European population?, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 142-142, ISSN: 0105-4538

Conference paper

Vila-Nadal G, Gunawardana N, Rey-Garcia H, Wheeler K, Durham SR, Scadding Get al., 2019, Successful intravaginal graded human seminal plasma desensitization in a Can F5 sensitized patient, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 706-707, ISSN: 0105-4538

Conference paper

Hull JH, Walsted ES, Feary J, Cullinan P, Scadding G, Bailey E, Selby Jet al., 2019, Continuous laryngoscopy during provocation in the assessment of inducible laryngeal obstruction, Laryngoscope, Vol: 129, Pages: 1863-1866, ISSN: 0023-852X

Journal article

Lenormand M, Layhadi JA, Hu J, Van Dick FA, Scadding G, Lavender P, Durham SR, Shamji MHet al., 2019, Epigenetic changes in SATB1 gene in FoxP3+regulatory T cells reflect immune tolerance status during grass pollen subcutaneous and sublingual immunotherapy, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 63-64, ISSN: 0105-4538

Conference paper

Heffler E, Brussino L, Del Giacco S, Paoletti G, Minciullo PL, Varricchi G, Scadding G, Malvezzi L, De Virgilio A, Spriano G, Puggioni F, Fornero M, Rolla G, Canonica GWet al., 2019, New drugs in early-stage clinical trials for allergic rhinitis, EXPERT OPINION ON INVESTIGATIONAL DRUGS, Vol: 28, Pages: 267-273, ISSN: 1354-3784

Journal article

Shamji MH, Layhadi JA, Achkova D, Kouser L, Perera-Webb A, Couto-Francisco NC, Parkin R, Matsuoka T, Scadding G, Ashton-Rickardt PG, Durham SRet al., 2019, Role of interleukin-35 in sublingual allergy immunotherapy, Journal of Allergy and Clinical Immunology, Vol: 143, Pages: 1131-1142.e4, ISSN: 0091-6749

BACKGROUND: Grass pollen-specific immunotherapy involves immunomodulation of allergen-specific T helper 2 cell (Th2) responses and induction of IL-10+ and/or TGF-β+CD4+CD25+ regulatory T cells (iTregs). IL-35+CD4+CD25+Foxp3- T (iTR35) cells have been reported as a novel subset of iTregs with modulatory characteristics. OBJECTIVE: To investigate the mechanisms underlying the induction and maintenance of immunological tolerance induced by IL-35 and iTR35 cells. METHODS: The biological effects of IL-35 was assessed on Group II innate lymphoid cells (ILC2s), dendritic cells (DCs) primed with TSLP, IL-25 and IL-33, B and Th2 cells by flow cytometry and qRT-PCR. Grass pollen-driven Th2 cell proliferation and cytokine production was measured by [3H]-thymidine and Luminex MagPix, respectively. iTr35 cells were quantified in grass pollen allergics (SAR, n=16), sublingual immunotherapy-treated patients (SLIT, n=16) and non-atopic controls (NAC, n=16). RESULTS: SAR had elevated proportions of ILC2s (P=.002), IL5+ (P=.042), IL13+ (P=.042) and IL5+IL13+ILC2s (P=.003) compared to NAC. IL-35 inhibited IL-5 and IL-13 production by ILC2s in the presence of IL-25 or IL-33 (P=.031) and allergen-driven Th2 cytokines by Teff cells. IL-35 inhibited CD40L, IL-4 and IL-21-mediated IgE production by B cells (P=.015), allergen-driven T cell proliferation (P=.001) and Th2 cytokine production by primed DCs. iTR35 cells suppressed Th2 cell proliferation and cytokine production. In addition, allergen-driven IL-35 levels and iTR35 cells were elevated in SLIT (all, P<.001) and NAC (all, P<.001) compared to SAR. CONCLUSION: IL-35 and iTR35 cells are potential novel immune-regulators induced by SLIT. The clinical relevance of SLIT may be underscored by the restoration of protective iTR35 cells.

Journal article

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