Imperial College London

ProfessorStephenDurham

Faculty of MedicineNational Heart & Lung Institute

Professor of Allergy and Respiratory Medicine
 
 
 
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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
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716 results found

Pfaar O, Agache I, Bergmann KC, 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., 2020, Placebo effects in allergen immunotherapy - an EAACI Task Force Position Paper., Allergy

The placebo (Latin "I will please") effect commonly occurs in clinical trials. The psychological and physiological factors associated with patients' expectations about a treatment's positive and negative effects have yet to be well characterized, although a functional prefrontal cortex and intense bidirectional communication between the central nervous system and the immune system appear to be prerequisites for a placebo effect. The use of placebo raises certain ethical issues, especially if patients in a placebo group are denied an effective treatment for a long period of time. The placebo effect appears to be relatively large (up to 77%, relative to pre-treatment scores) in controlled clinical trials of allergen immunotherapy (AIT), such as the pivotal, double-blind, placebo-controlled (DBPC) randomized clinical trials currently required by regulatory authorities worldwide. The European Academy of Allergy and Clinical Immunology (EAACI) therefore initiated a Task Force, in order to better understand the placebo effect in AIT and its specific role in comorbidities, blinding issues, adherence, measurement time points, variability, and the natural course of the disease. In this Position Paper, the EAACI Task Force highlights several important topics regarding the placebo effect in AIT such as i) regulatory aspects, ii) neuroimmunological and psychological mechanisms, iii) placebo effect sizes in AIT trials, iv) methodological limitations in AIT trial design and v) potential solutions in future AIT trial design. In conclusion, this Position Paper aims to examine the methodological problem of placebo in AIT from different aspects and also to highlight unmet needs and possible solutions for future trials.

Journal article

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., J Allergy Clin Immunol

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, Larché 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., J Allergy Clin Immunol

BACKGROUND: The direct-instillation nasal allergen challenge (NAC) and the environmental exposure chamber (EEC) are 2 methods of conducting controlled allergen provocations. The clinical and biological comparability of these methods has not been thoroughly investigated. OBJECTIVE: We sought to compare clinical and immunologic responses to cat allergen in NAC versus EEC. METHODS: Twenty-four participants were randomized to receive either NAC followed by a 2-day challenge in an EEC or a 2-day challenge in an EEC followed by NAC. Challenges were separated by 28-day washout periods. We measured total nasal symptom scores, peak nasal inspiratory flow, nasal (0-8 hours) and serum cytokines, serum antibodies, peripheral blood antigen-specific T lymphocytes, and gene expression in nasal scrapings. The primary outcome was the total nasal symptom score area under the curve for the first 3 hours after allergen exposure in NAC or after initiation of exposure in EEC. RESULTS: Both challenges increased IL-5 and IL-13 in nasal fluids and serum and resulted in altered nasal cell expression of gene modules related to mucosal biology and transcriptional regulation. Changes in gene modules, more so than cytokine measurements, showed significant associations with total nasal symptom score and peak nasal inspiratory flow. Overall, EEC exposure generated larger responses and more early terminations compared with NAC. Although the 2 challenges did not correlate in symptom magnitude or temporality, striking correlations were observed in cytokine levels. CONCLUSIONS: Although clinical outcomes of NAC and EEC were temporally different and nonequivalent in magnitude, immunologic responses were similar. Selection of a particular allergen challenge method should depend on considerations of study objectives and cost.

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, ISSN: 0105-4538

Journal article

Patel K, Vila-Nadal G, Shah J, Shamji M, Swan L, Durham SR, Patel K, Skypala IJet al., 2020, Is pollen-food syndrome a frequent comorbidity in adults with irritable bowel syndrome?, ALLERGY, ISSN: 0105-4538

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

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

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., Allergen-specific IgG+ memory B cells are temporally linked to IgE memory responses, Journal of Allergy and Clinical Immunology, 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

Pfaar O, Agache I, de Blay F, Bonini S, Chaker AM, Durham SR, Gawlik R, Hellings PW, Jutel M, Kleine-Tebbe J, Klimek L, Kopp MV, Nandy A, Rabin RL, Van Ree R, Renz H, Roberts G, Salapatek A-M, Schmidt-Weber CB, Shamji MH, Sturm GJ, Virchow JC, Wahn U, Willers C, Zieglmayer P, Akdis CAet al., 2019, Perspectives in allergen immunotherapy: 2019 and beyond, ALLERGY, Vol: 74, Pages: 3-25, ISSN: 0105-4538

Journal article

Penagos M, Durham SR, 2019, Duration of allergen immunotherapy for inhalant allergy, CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 19, Pages: 594-605, ISSN: 1528-4050

Journal article

Nasser S, Whyte AF, Durham SR, Krishna MTet al., 2019, Switch-over from Pharmalgen to Alutard Bee and Wasp venom in the UK., Clin Exp Allergy, Vol: 49, Pages: 1645-1646

Journal article

Dua S, Ruiz-Garcia M, Bond S, Durham SR, Kimber I, Mills C, Roberts G, Skypala I, Wason J, Ewan P, Boyle R, Clark Aet al., 2019, The effect of sleep deprivation and exercise on reaction threshold in peanut-allergic adults: a randomised controlled study, Journal of Allergy and Clinical Immunology, Vol: 144, Pages: 1584-1594.e2, ISSN: 0091-6749

BACKGROUND: Peanut allergy causes severe and fatal reactions. Current food allergen labelling fails to address these risks adequately against the burden of restricting food choice for allergic individuals because of limited data on thresholds of reactivity and the influence of everyday factors. OBJECTIVE: We estimated peanut threshold doses for a UK peanut-allergic population and examined the effect of sleep deprivation and exercise. METHOD: In a crossover study, following blinded challenge, peanut-allergic participants underwent three open peanut challenges in random order: with exercise following each dose, with sleep deprivation preceding challenge, and with no intervention. Primary outcome was the threshold dose triggering symptoms (mg protein). Primary analysis estimated the difference between non-intervention challenge and each intervention in log threshold (as % change). Dose distributions were modelled deriving eliciting doses in the peanut-allergic population. RESULTS: Baseline challenges were performed in 126 subjects, 100 were randomized and 81 (mean age 25y) completed at least one further challenge. The mean (SD) threshold was 214 mg (330mg) for non-intervention challenges and this was reduced by 45% (95% confidence interval 21,61 p=0.001) and 45% (22,62 p=0.001) for exercise and sleep deprivation, respectively. Mean (95% confidence interval) estimated eliciting doses for 1% of the population were 1.5mg (0.8,2.5) during non-intervention challenge (n=81), 0.5mg (0.2,0.8) following sleep and 0.3mg (0.1,0.6) following exercise. CONCLUSION: Exercise and sleep deprivation each significantly reduce the threshold of reactivity in people with peanut allergy, putting them at greater risk of a reaction. Adjusting reference doses using these data will improve allergen risk-management and labelling to optimize protection of peanut-allergic consumers.

Journal article

Hj Awg Sharif H, Singh I, Kouser L, Mösges R, Bonny M-A, Karamani A, Parkin R, Bovy N, Kishore U, Robb A, Katotomichelakis M, Holtappels G, Derycke L, Corazza F, von Frenckell R, Wathelet N, Duchateau J, Legon T, Pirotton S, Durham S, Bachert C, Shamji Met al., 2019, Immunologic mechanisms of short-course of Lolium Perenne peptide immunotherapy: a randomized double-blind placebo-controlled trial, Journal of Allergy and Clinical Immunology, Vol: 144, Pages: 738-749, ISSN: 0091-6749

BackgroundThree-week, short-course of adjuvant-free hydrolysates of Lolium perenne peptide (LPP) immunotherapy for rhinoconjunctivitis with/without asthma over 4 physician visits is safe, well-tolerated and effective.ObjectiveTo investigate immunologic mechanisms of LPP immunotherapy in a subset of patients who participated in a Phase III, multicenter, randomized, double-blind, placebo-controlled trial (clinical.gov NCT02560948).MethodsParticipants were randomized to receive LPP (n=21) or placebo (PL; n=11) for 3 weeks over 4 visits. Grass pollen-induced basophil, T and B cell responses were evaluated before (V2), end of treatment (V6) and after the pollen season (V8).ResultsCombined symptom and rescue medication scores (CSMS) were lower during the peak (-35.1%, P=.03) and throughout pollen season (-53.7%, P=.03) in LPP- compared to PL-treated group. CD63+ and CD203cbrightCRTH2+basophils were decreased following LPP treatment at V6 (all, P<.0001) and V8 (all, P<.001), compared to V2. No change in PL-treated group was observed. Blunting of seasonal increases of grass pollen-specific IgE was observed in LPP- but not PL-treated group. LPP immunotherapy but not PL was associated with a reduction of IL-4+ Th2 (V6, P=.02), IL-4+ (V6, P=.001;V8, P=.0095) and IL-21+ (V6, P=.0002) T follicular helper cells. Induction of FoxP3+, follicular regulatory T and IL-10+ Breg cells were observed at V6 (all, P<.05) and V8 (all, P<.05) in LPP-treated group. Induction of regulatory B cells was associated with allergen neutralizing IgG4 blocking antibodies.ConclusionFor the first time, we demonstrate that the immunological mechanisms of LPP immunotherapy are underscored by immune modulation in the T and B cell compartments which is necessary for its effect.

Journal article

Bousquet J, Nhan P-T, Bedbrook A, Agache I, Annesi-Maesano I, Ansotegui I, Anto JM, Bachert C, Benveniste S, Bewick M, Billo N, Bosnic-Anticevich S, Bosse I, Brusselle G, Calderon MA, Canonica GW, Caraballo L, Cardona V, Maria Carriazo A, Cash E, Cecchi L, Chu DK, Colgan E, Costa E, Cruz AA, Czarlewski W, Durham S, Ebisawa M, Erhola M, Fauquert J-L, Fokkens WJ, Fonseca JA, Guldemond N, Iinuma T, Illario M, Klimek L, Kuna P, Kvedariene V, Larenas-Linneman D, Laune D, Le LTT, Lourenco O, Malva JO, Marien G, Menditto E, Mullol J, Munter L, Okamoto Y, Onorato GL, Papadopoulos NG, Perala M, Pfaar O, Phillips A, Phillips J, Pinnock H, Portejoie F, Quinones-Delgado P, Rolland C, Rodts U, Samolinski B, Sanchez-Borges M, Schunemann HJ, Shamji M, Somekh D, Togias A, Toppila-Salmi S, Tsiligianni I, Usmani O, Walker S, Wallace D, Valiulis A, Van der Kleij R, Ventura MT, Williams S, Yorgancioglu A, Zuberbier Tet al., 2019, Next-generation care pathways for allergic rhinitis and asthma multimorbidity: a model for multimorbid non-communicable diseases-Meeting Report (Part 2), JOURNAL OF THORACIC DISEASE, Vol: 11, Pages: 4072-4084, ISSN: 2072-1439

Journal article

Bousquet J, Pfaar O, Togias A, Schunemann HJ, Ansotegui I, Papadopoulos NG, Tsiligianni I, Agache I, Anto JM, Bachert C, Bedbrook A, Bergmann KC, Bosnic-Anticevich S, Bosse I, Brozek J, Calderon M, Canonica GW, Caraballo L, Cardona V, Casale T, Cecchi L, Chu DK, Costa E, Cruz AA, Czarlewski W, Durham SR, Du Toit G, Dykewicz M, Ebisawa M, Fauquert JL, Fernandez-Rivas M, Fokkens WJ, Fonseca J, Fontaine JF, van Wijk RG, Haahtela T, Halken S, Hellings PW, Ierodiakonou D, Iinuma T, Ivancevich JC, Jacobsen L, Jutel M, Kaidashev I, Khaitov M, Kalayci O, Tebbe JK, Klimek L, Kowalski ML, Kuna P, Kvedariene V, La Grutta S, Larenas-Linemann D, Lau S, Laune D, Le L, Carlsen KL, Lourenco O, Malling HJ, Marien G, Menditto E, Mercier G, Mullol J, Muraro A, O'Hehir R, Okamoto Y, Pajno GB, Park HS, Panzner P, Passalacqua G, Pham-Thi N, Roberts G, Rolland C, Rosario N, Ryan D, Samolinski B, Sanchez-Borges M, Scadding G, Shamji MH, Sheikh A, Sturm GJ, Bom AT, Toppila-Salmi S, Valentin-Rostan M, Valiulis A, Valovirta E, Ventura MT, Wahn U, Walker S, Wallace D, Waserman S, Yorgancioglu A, Zuberbier Tet al., 2019, 2019 ARIA Care pathways for allergen immunotherapy, ALLERGOLOGIE, Vol: 42, Pages: 404-425, ISSN: 0344-5062

Journal article

Sahiner UM, Durham SR, 2019, Hymenoptera Venom Allergy: How Does Venom Immunotherapy Prevent Anaphylaxis From Bee and Wasp Stings?, FRONTIERS IN IMMUNOLOGY, Vol: 10, ISSN: 1664-3224

Journal article

Bousquet J, Nhan P-T, Bedbrook A, Agache I, Annesi-Maesano I, Ansotegui I, Anto JM, Bachert C, Benveniste S, Bewick M, Billo N, Bosnic-Anticevich S, Bosse I, Brusselle G, Calderon MA, Canonica GW, Caraballo L, Cardona V, Maria Carriazo A, Cash E, Cecchi L, Chu DK, Colgan E, Costa E, Cruz AA, Czarlewski W, Durham S, Ebisawa M, Erhola M, Fauquert J-L, Fokkens WJ, Fonseca JA, Guldemond N, Iinuma T, Illario M, Klimek L, Kuna P, Kvedariene V, Larenas-Linneman D, Laune D, Le LTT, Lourenco O, Malva JO, Marien G, Menditto E, Mullol J, Munter L, Okamoto Y, Onorato GL, Papadopoulos NG, Perala M, Pfaar O, Phillips A, Phillips J, Pinnock H, Portejoie F, Quinones-Delgado P, Rolland C, Rodts U, Samolinski B, Sanchez-Borges M, Schunemann HJ, Shamji M, Somekh D, Togias A, Toppila-Salmi S, Tsiligianni I, Usmani O, Walker S, Wallace D, Valiulis A, Van der Kleij R, Ventura MT, Williams S, Yorgancioglu A, Zuberbier Tet al., 2019, Next-generation care pathways for allergic rhinitis and asthma multimorbidity: a model for multimorbid non-communicable diseases, JOURNAL OF THORACIC DISEASE, Vol: 11, Pages: 3633-3641, ISSN: 2072-1439

Journal article

Shamji MH, Thomsen I, Layhadi JA, Kappen J, Holtappels G, Sahiner U, Switzer A, Durham SR, Pabst O, Bachert Cet al., 2019, Broad immunglobulin G repertoire in chronic rhinosinusitis with nasal polyps regulates pro-inflammatory IgE responses, Journal of Allergy and Clinical Immunology, Vol: 143, Pages: 2086-2094.e2, ISSN: 0091-6749

BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is often characterized by local production of polyclonal IgE-idiotypes. Whilst tissue IgE concentrations can be in the range of several thousand kU/L, the regulatory mechanisms by which IgE-mediated inflammation is controlled in the nasal polyps is not well understood.ObjectiveWe sought to determine whether locally induced IgG antibodies in the nasal polyps can inhibit IgE-mediated pro-allergic response.MethodsNasal polyp homogenates were collected from grass pollen allergics with CRSwNP and non-allergic controls. IgE levels were measured by ISAC. IgE-containing nasal polyp homogenates, with/without IgG depletion, were evaluated for their capacity to promote IgE-facilitated allergen presentation, basophil activation and histamine release. Local IgE and IgG repertoires were evaluated by Immunoglobulin 454 sequencing.ResultsWe show that IgG plays a key role in controlling IgE-mediated inflammatory responses in nasal polyps. Depletion of IgG from nasal homogenates resulted in an increase in CD23-mediated IgE-facilitated allergen binding to B cells (IgE-FAB), but also enhanced FcεRI-mediated allergen driven basophil activation and histamine release. A similar response was observed in relation to specific IgE antibodies to Staphylococcus aureus (SE-IgE). The capacity of IgG in nasal polyps to limit IgE-mediated inflammation is based on the fact that IgG repertoires widely share the antigen targets with the IgE repertoires, in both allergic and non-allergic subjects.ConclusionPolyclonal IgE idiotypes in CRSwNP are functional, promote IgE-mediated pro-allergic inflammation and are partially antagonized by corresponding IgG-idiotypes. This is most likely due to the fact that IgE and IgG clonotypes are widely shared in nasal polyps.

Journal article

Wheatley LM, Wood R, Nadeau K, Liu A, Zoratti E, Bacharier L, Brittain E, Calderon M, Casale T, Chipps B, Cox L, Creticos PS, Desai M, Dreborg S, Durham S, Gergen PJ, Gruchalla R, Nelson H, O'Hehir RE, Plaut M, Schwaninger JM, Tilles S, Vickery B, Wittenberg KM, Togias Aet al., 2019, Mind the gaps: Clinical trial concepts to address unanswered questions in aeroallergen immunotherapy-An NIAID/AHRQ Workshop, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 143, Pages: 1711-1726, ISSN: 0091-6749

Journal article

Philpott C, le Conte S, Beard D, Cook J, Sones W, Morris S, Clarke CS, Thomas M, Little P, Vennik J, Lund V, Blackshaw H, Schilder A, Durham S, Denaxas S, Carpenter J, Boardman J, Hopkins Cet al., 2019, Clarithromycin and endoscopic sinus surgery for adults with chronic rhinosinusitis with and without nasal polyps: study protocol for the MACRO randomised controlled trial, TRIALS, Vol: 20, ISSN: 1745-6215

Journal article

Blackshaw H, Vennik J, Philpott C, Thomas M, Eyles C, Carpenter J, Clarke CS, Morris S, Schilder A, Lund V, Little P, Durham S, Denaxas S, Williamson E, Beard D, Cook J, Le Conte S, Airey K, Boardman J, Hopkins Cet al., 2019, Expert panel process to optimise the design of a randomised controlled trial in chronic rhinosinusitis (the MACRO programme), TRIALS, Vol: 20, ISSN: 1745-6215

Journal article

Durham SR, 2019, The allergen-specificity of allergen immunotherapy - doubt no more., Allergy

The ARIA-GA2LEN collaboration published a guide for the design and evaluation of randomised controlled trials of allergen immunotherapy for allergic rhinitis. Several problems in were identified. For example, the severity/persistence of seasonal symptoms in subjects during allergen immunotherapy was noted to be much lower than in trials of pharmacotherapy. The drop-out rates were higher. Seasonal pollen counts varied markedly between study centres and year-on-year during long-term trials thereby confounding the ability to detect treatment effects during 'low' pollen seasons. Placebo unmasking occurred due to the local side effects of allergen immunotherapy in actively treated participants. This article is protected by copyright. All rights reserved.

Journal article

Bousquet J, Pfaar O, Togias A, Schünemann HJ, Ansotegui I, Papadopoulos NG, Tsiligianni I, Agache I, Anto JM, Bachert C, Bedbrook A, Bergmann KC, Bosnic-Anticevich S, Bosse I, Brozek J, Calderon M, Canonica GW, Caraballo L, Cardona V, Casale T, Cecchi L, Chu DK, Costa E, Cruz AA, Czarlewski W, Durham SR, Du Toit G, Dykewicz M, Ebisawa M, Fauquert JL, Fernandez-Rivas M, Fokkens WJ, Fonseca J, Fontaine JF, van Wijk RG, Haahtela T, Halken S, Hellings PW, Ierodiakonou D, Iinuma T, Ivancevich JC, Jacobsen L, Jutel M, Kaidashev I, Khaitov M, Kalayci O, Kleine Tebbe J, Klimek L, Kowalski ML, Kuna P, Kvedariene V, La Grutta S, Larenas-Linemann D, Lau S, Laune D, Le L, Carlsen KL, Lourenço O, Malling HJ, Marien G, Menditto E, Mercier G, Mullol J, Muraro A, O'Hehir R, Okamoto Y, Pajno GB, Park HS, Panzner P, Passalacqua G, Pham-Thi N, Roberts G, Rolland C, Rosario N, Ryan D, Samolinski B, Sanchez-Borges M, Scadding G, Shamji MH, Sheikh A, Sturm GJ, Todo Bom A, Toppila-Salmi S, Valentin-Rostan M, Valiulis A, Valovirta E, Ventura MT, Wahn U, Walker S, Wallace D, Waserman S, Yorgancioglu A, Zuberbier T, ARIA Working Groupet al., 2019, 2019 ARIA Care pathways for allergen immunotherapy., Allergy

Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence-based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including health professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as on the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow up of patients. This article is protected by copyright. All rights reserved.

Journal article

Menditto E, Costa E, Midão L, Bosnic-Anticevich S, Novellino E, Bialek S, Briedis V, Mair A, Rajabian-Soderlund R, Arnavielhe S, Bedbrook A, Czarlewski W, Annesi-Maesano I, Anto JM, Devillier P, De Vries G, Keil T, Sheikh A, Orlando V, Larenas-Linnemann D, Cecchi L, De Feo G, Illario M, Stellato C, Fonseca J, Malva J, Morais-Almeida M, Pereira AM, Todo-Bom A, Kvedariene V, Valiulis A, Bergmann KC, Klimek L, Mösges R, Pfaar O, Zuberbier T, Cardona V, Mullol J, Papadopoulos NG, Prokopakis EP, Bewick M, Ryan D, Roller-Wirnsberger RE, Tomazic PV, Cruz AA, Kuna P, Samolinski B, Fokkens WJ, Reitsma S, Bosse I, Fontaine JF, Laune D, Haahtela T, Toppila-Salmi S, Bachert C, Hellings PW, Melén E, Wickman M, Bindslev-Jensen C, Eller E, O'Hehir RE, Cingi C, Gemicioğlu B, Kalayci O, Ivancevich JC, Bousquet J, MASK groupet al., 2019, Adherence to treatment in allergic rhinitis using mobile technology. the mask study, Clinical and Experimental Allergy, Vol: 49, Pages: 442-460, ISSN: 0954-7894

BACKGROUND: Mobile technology may help to better understand the adherence to treatment MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centered ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. OBJECTIVES: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. METHODS: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from January 1, 2016 to August 1, 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. RESULTS: 12,143 users were registered. 6,949 users reported at least one VAS data recording. Among them, 1,887 users reported ≥ 7 VAS data. 1,195 subjects were included in the analysis of adherence. 136 (11.28%) users were adherent (MPR ≥70% and PDC ≤ 1.25), 51 (4.23%) were partly adherent (MPR ≥70% and PDC =1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR<70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users. CONCLUSION AND CLINICAL RELEVANCE: Adherence to treatment is low. The relative efficacy of continuous versus on-demand treatment for AR symptoms is still a matter of debate.This study shows an approach for measuring retrospective adherence based on a mobile app. This represent a novel approach also for analyzing medication taking behavior in a real-world setting. This article is protected by copyright. All rights reserved.

Journal article

Bousquet J, Bedbrook A, Czarlewski W, Onorato GL, Arnavielhe S, Laune D, Mathieu-Dupas E, Fonseca J, Costa E, Lourenco O, Morais-Almeida M, Todo-Bom A, Illario M, Menditto E, Canonica GW, Cecchi L, Monti R, Napoli L, Ventura MT, De Feo G, Fokkens WJ, Chavannes NH, Reitsma S, Cruz AA, da Silva J, Serpa FS, Larenas-Linnemann D, Perez JMF, Huerta-Villalobos YR, Rivero-Yeverino D, Rodriguez-Zagal E, Valiulis A, Dubakiene R, Emuzyte R, Kvedariene V, Annesi-Maesano I, Blain H, Bonniaud P, Bosse I, Dauvilliers Y, Devillier P, Fontaine JF, Pepin JL, Pham-Thi N, Portejoie F, Picard R, Roche N, Rolland C, Schmidt-Grendelmeier P, Kuna P, Samolinski B, Anto JM, Cardona V, Mullol J, Pinnock H, Ryan D, Sheikh A, Walker S, Williams S, Becker S, Klimek L, Pfaar O, Bergmann KC, Mosges R, Zuberbier T, Roller-Wirnsberger RE, Tomazic PV, Haahtela T, Salimaki J, Toppila-Salmi S, Valovirta E, Vasankari T, Gemicioglu B, Yorgancioglu A, Papadopoulos NG, Prokopakis EP, Tsiligianni IG, Bosnic-Anticevich S, O'Hehir R, Ivancevich JC, Neffen H, Zernotti ME, Kull I, Melen E, Wickman M, Bachert C, Hellings PW, Brusselle G, Palkonen S, Bindslev-Jensen C, Eller E, Waserman S, Boulet LP, Bouchard J, Chu DK, Schunemann HJ, Sova M, De Vries G, van Eerd M, Agache I, Ansotegui IJ, Bewick M, Casale T, Dykewick M, Ebisawa M, Murray R, Naclerio R, Okamoto Y, Wallace DV, Bousquet J, Hellings PW, Aberer W, Agache I, Akdis CA, Akdis M, Aliberti MR, Almeida R, Amat F, Angles R, Annesi-Maesano I, Ansotegui IJ, Anto JM, Arnavielle S, Asayag E, Asarnoj A, Arshad H, Avolio F, Bacci E, Bachert C, Baiardini I, Barbara C, Barbagallo M, Baroni I, Barreto BA, Basagana X, Bateman ED, Bedolla-Barajas M, Bedbrook A, Bewick M, Beghe B, Bel EH, Bergmann KC, Bennoor KS, Benson M, Bertorello L, Bialoszewski AZ, Bieber T, Bialek S, Bindslev-Jensen C, Bjermer L, Blain H, Blasi F, Blua A, Marciniak MB, Bogus-Buczynska I, Boner AL, Bonini M, Bonini S, Bosnic-Anticevich CS, Bosse I, Bouchard J, Boulet LP, Bourret R, Bousquet PJ Bet al., 2019, Guidance to 2018 good practice: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma, CLINICAL AND TRANSLATIONAL ALLERGY, Vol: 9, ISSN: 2045-7022

AimsMobile Airways Sentinel NetworK (MASK) belongs to the Fondation Partenariale MACVIA-LR of Montpellier, France and aims to provide an active and healthy life to rhinitis sufferers and to those with asthma multimorbidity across the life cycle, whatever their gender or socio-economic status, in order to reduce health and social inequities incurred by the disease and to improve the digital transformation of health and care. The ultimate goal is to change the management strategy in chronic diseases.MethodsMASK implements ICT technologies for individualized and predictive medicine to develop novel care pathways by a multi-disciplinary group centred around the patients.StakeholdersInclude patients, health care professionals (pharmacists and physicians), authorities, patient’s associations, private and public sectors.ResultsMASK is deployed in 23 countries and 17 languages. 26,000 users have registered.

Journal article

Bousquet J, Hellings PW, Agache I, Amat F, Annesi-Maesano I, Ansotegui IJ, Anto JM, Bachert C, Bateman ED, Bedbrook A, Bennoor K, Bewick M, Bindslev-Jensen C, Bosnic-Anticevich S, Bosse I, Brozek J, Brussino L, Canonica GW, Cardona V, Casale T, Sarabia AMC, Chavannes NH, Cecchi L, de Sousa JC, Costa E, Cruz AA, Czarlewski W, De Carlo G, De Feo G, Demoly P, Devillier P, Dykewicz MS, El-Gamal Y, Eller EE, Fonseca JA, Fontaine J-F, Fokkens WJ, Guzman M-A, Haahtela T, Illario M, Ivancevich J-C, Just J, Kaidashev I, Khaitov M, Kalayci O, Keil T, Klimek L, Kowalski ML, Kuna P, Kvedariene V, Larenas-Linnemann D, Laune D, Le LTT, Carlsen KL, Lourenco O, Mahboub B, Mair A, Menditto E, Milenkovic B, Morais-Almeida M, Mosges R, Mullol J, Murray R, Naclerio R, Namazova-Baranova L, Novellino E, O'Hehir RE, Ohta K, Okamoto Y, Okubo K, Onorato GL, Palkonen S, Panzner P, Papadopoulos NG, Park H-S, Paulino E, Pawankar R, Pfaar O, Plavec D, Popov TA, Potter P, Prokopakis EP, Rottem M, Ryan D, Salimaki J, Samolinski B, Sanchez-Borges M, Schunemann HJ, Sheikh A, Sisul J-C, Rajabian-Soderlund R, Sooronbaev T, Stellato C, To T, Todo-Bom A-M, Tomazic P-V, Toppila-Salmi S, Valero A, Valiulis A, Valovirta E, Ventura M-T, Wagenmann M, Wang DY, Wallace D, Waserman S, Wickman M, Yorgancioglu A, Zhang L, Zhong N, Zidarn M, Zuberbier T, Bousquet J, Hellings PW, Aberer W, Agache I, Akdis CA, Akdis M, Alberti MR, Almeida R, Amat F, Angles R, Annesi-Maesano I, Ansotegui IJ, Anto JM, Arnavielle S, Asayag E, Asarnoj A, Arshad H, Avolio F, Bacci E, Bachert C, Baiardini I, Barbara C, Barbagallo M, Baroni I, Barreto BA, Basagana X, Bateman ED, Bedolla-Barajas M, Bedbrook A, Bewick M, Beghe B, Bel EH, Bergmann KC, Bennoor KS, Benson M, Bertorello L, Biaoszewski AZ, Bieber T, Bialek S, Bindslev-Jensen C, Bjermer L, Blain H, Blasi F, Blua A, Marciniak MB, Bogus-Buczynska I, Boner AL, Bonini M, Bonini S, Bosnic-Anticevich CS, Bosse I, Bouchard J, Boulet LP, Bourret R, Bousquet PJ, Braido F, Briedis V, Brighet al., 2019, Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018): Change management in allergic rhinitis and asthma multimorbidity using mobile technology, Journal of Allergy and Clinical Immunology, Vol: 143, Pages: 864-879, ISSN: 0091-6749

Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.

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

Shamji MH, Kappen J, Abubakar-Waziri H, Zhang J, Steveling E, Watchman S, Kouser L, Eifan A, Switzer A, Varrichi G, Marone G, Couto-Francisco NC, Calderon M, Durham SRet al., 2019, Nasal allergen neutralising IgG4 antibodies block IgE-mediated responses: novel biomarker of subcutaneous grass pollen immunotherapy, Journal of Allergy and Clinical Immunology, Vol: 143, Pages: 1067-1076, ISSN: 0091-6749

BACKGROUND: Grass pollen subcutaneous immunotherapy (SCIT) is associated with induction of serum IgG4-associated inhibitory antibodies that prevent IgE-facilitated allergen binding to B cells. OBJECTIVE: To determine whether SCIT induces nasal allergen-specific IgG4 antibodies with inhibitory activity that correlate closely with clinical response. METHODS: In a cross-sectional, controlled study, nasal fluid and sera were collected during the grass pollen season from 10 SCIT-treated patients, 13 untreated allergics (SAR) and 12 non-atopic controls (NA). Nasal and serum IgE and IgG4 to Phleum pratense (Phl p) components were measured by ISAC microarray. Inhibitory activity was measured by IgE-FAB assay. IL-10+Breg cells were quantified in peripheral blood by flow cytometry. RESULTS: Nasal and serum Phl p1 and Phl p5-specific IgE levels were elevated in SAR compared to NA (all, P < .001) and SCIT group. Nasal IgG4 levels were increased in SCIT compared to SAR group (P < .001) during the pollen season compared to out of season. IgG-associated inhibitory activity in nasal fluid and serum was significantly increased in SCIT compared to SAR group (both, P < .001). The magnitude of the inhibitory activity was 96% in the nasal fluid compared to 66% in serum and was reversed following depletion of IgG in nasal fluid (P = .03) and serum (P = .002). Both nasal fluid (r = -0.67, P = .0011) and serum (r = -0.59, P = .0097) blocking activity correlated global symptom improvement. IL-10+Breg cells were increased in season compared to out of season in SCIT group (P < .01). CONCLUSION: For the first time, we show that nasal IgG4-associated inhibitory activity correlate closely with the clinical response to allergen immunotherapy in allergic rhinitis with/without asthma.

Journal article

Dua S, Garcia MR, Bond S, Durham SR, Kimber I, Mills C, Roberts G, Skypala IJ, Wason J, Ewan PW, Boyle RJ, Clark ATet al., 2019, Reaction thresholds in in peanut-allergic adults and the influence of exercise and sleep deprivation: a randomised controlled trial, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB202-AB202, ISSN: 0091-6749

Conference paper

Turner PJ, Patel N, Ruiz-Garcia M, Skypala IJ, Durham SR, Boyle RJ, Wang KY, Wu S, Li H, Spergel JMet al., 2019, Changes in Whole Blood Transcriptome during Peanut-Induced Anaphylaxis and Correlation with Symptoms, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB423-AB423, ISSN: 0091-6749

Conference paper

Calderon MA, Carr VA, Jacobson M, Sheikh A, Durham Set al., 2019, Allergen injection immunotherapy for perennial allergic rhinitis, Cochrane Database of Systematic Reviews, Vol: 2019

© 2019 The Cochrane Collaboration. This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To evaluate the effectiveness and safety of injection immunotherapy in treating perennial allergic rhinitis.

Journal article

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