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Layhadi JA, Paques C, Destine A, et al., 2019, The allergenicity and immunogenicity of peanut and house dust mite peptides generated by a novel technology platform: The future of immunotherapy treatments, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 117-118, ISSN: 0105-4538
Kirtland M, Vila-Nadal G, Tsitoura D, et al., 2019, A novel toll-like receptor 7 agonist can ameliorate phleum pratense induced allergic responses in vitro, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 80-80, ISSN: 0105-4538
Vila-Nadal G, Gunawardana N, Rey-Garcia H, et 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
Shamji MH, Thomsen I, Layhadi JA, et 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.
Wheatley LM, Wood R, Nadeau K, et 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
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- Citations: 17
Philpott C, le Conte S, Beard D, et 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
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- Citations: 12
Blackshaw H, Vennik J, Philpott C, et 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
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- Citations: 4
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.
Bousquet J, Pfaar O, Togias A, et 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.
Menditto E, Costa E, Midão L, et 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.
Bousquet J, Bedbrook A, Czarlewski W, et 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.
Bousquet J, Hellings PW, Agache I, et 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.
Shamji MH, Kappen J, Abubakar-Waziri H, et 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.
Shamji MH, Layhadi JA, Achkova D, et 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.
Turner PJ, Patel N, Ruiz-Garcia M, et 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
Dua S, Garcia MR, Bond S, et 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
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- Citations: 1
Calderon MA, Carr VA, Jacobson M, et 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.
Frew AJ, Ljørring C, Wolf H, et al., 2018, UK Immunotherapy Study: reanalysis by a combined symptom and medication score, Journal of Allergy and Clinical Immunology, Vol: 142, Pages: 1998-1999.e3, ISSN: 0091-6749
Reanalysis of UK22 subcutaneous immunotherapy trial according to WAO/EAACI recommendations revealed clinically relevant improvements at both doses. Starting at the lower dose should enable efficacy with lower risk of adverse events.
Ntavli E, Sahiner UM, Layhadi J, et al., 2018, Group 2 innate lymphoid cells (ILC2s) contribute to the pathophysiology of Peanut Allergy, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1528-1528, ISSN: 0954-7894
Hug O, Singh I, Robb A, et al., 2018, IL-35 induces IL-10 producing Regulatory B cells in immunotherapy treated patients, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1548-1548, ISSN: 0954-7894
Dua S, Garcia MR, Bond S, et al., 2018, Reactivity thresholds in peanut allergic adults and the influence of stress and exercise: a randomised controlled trial, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1524-1524, ISSN: 0954-7894
Patel K, Vila-Nadal G, Shah J, et al., 2018, The prevalence of pollen food syndrome in adults with irritable bowel syndrome, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1537-1538, ISSN: 0954-7894
Garcia HR, Gunawardana N, Wheeler K, et al., 2018, Can component resolved diagnosis predict the outcome of oral food challenge to hazelnut?, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1547-1547, ISSN: 0954-7894
Layhadi J, Hu J, van Dijck A, et al., 2018, SATB1 expression and methylation reflect FOXP3<SUP>+</SUP> regulatory T cell activity during grass pollen immunotherapy, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1549-1549, ISSN: 0954-7894
Tang J, Singh I, Parkin R, et al., 2018, Clinical and immunologic effects of a single dose of Anti-Fel d 1-IgG4 monoclonal antibodies in cat allergic individuals: a double blind randomized placebo-controlled study, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1528-1528, ISSN: 0954-7894
Layhadi JA, Achkova D, Kouser L, et al., 2018, Interleukin-35 regulates type II-mediated responses elicited by innate lymphoid cells in allergic diseases, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1548-1549, ISSN: 0954-7894
Kirtland M, Tsitoura D, Durham S, et al., 2018, An in vitro assay to screen Toll-like Receptor agonists as potential adjuvants in allergen immunotherapy, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1527-1527, ISSN: 0954-7894
Bousquet J, Arnavielhe S, Bedbrook A, et al., 2018, MASK 2017: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma multimorbidity using real-world-evidence, Clinical and Translational Allergy, Vol: 8, ISSN: 2045-7022
mHealth, such as apps running on consumer smart devices is becoming increasingly popular and has the potential to profoundly affect healthcare and health outcomes. However, it may be disruptive and results achieved are not always reaching the goals. Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline using the best evidence-based approach to care pathways suited to real-life using mobile technology in allergic rhinitis (AR) and asthma multimorbidity. Patients largely use over-the-counter medications dispensed in pharmacies. Shared decision making centered around the patient and based on self-management should be the norm. Mobile Airways Sentinel networK (MASK), the Phase 3 ARIA initiative, is based on the freely available MASK app (the Allergy Diary, Android and iOS platforms). MASK is available in 16 languages and deployed in 23 countries. The present paper provides an overview of the methods used in MASK and the key results obtained to date. These include a novel phenotypic characterization of the patients, confirmation of the impact of allergic rhinitis on work productivity and treatment patterns in real life. Most patients appear to self-medicate, are often non-adherent and do not follow guidelines. Moreover, the Allergy Diary is able to distinguish between AR medications. The potential usefulness of MASK will be further explored by POLLAR (Impact of Air Pollution on Asthma and Rhinitis), a new Horizon 2020 project using the Allergy Diary.
Shamji MH, Ceuppens J, Bachert C, et al., 2018, Lolium perenne peptides for treatment of grass pollen allergy: a randomized, double-blind, placebo-controlled clinical trial, Journal of Allergy and Clinical Immunology, Vol: 141, Pages: 448-+, ISSN: 0091-6749
Mösges R, Bachert C, Panzner P, et al., 2018, Short-course of grass allergen peptides immunotherapy over three weeks reduces seasonal symptoms in allergic rhinoconjunctivitis with/without Asthma: A randomized, multicenter, double-blind, placebo-controlled trial, Allergy, Vol: 73, Pages: 1842-1850, ISSN: 0105-4538
BACKGROUND: Immunotherapy with peptide hydrolysates from Lolium perenne (LPP) is an alternative treatment for seasonal allergic rhinitis with or without asthma. The aim of this study was to assess the clinical efficacy and safety of a cumulative dose of 170 μg LPP administered subcutaneously over 3 weeks. METHODS: In a randomized, double blind, placebo-controlled trial, 554 adults with grass pollen rhinoconjunctivitis were randomized (1:2 ratio) to receive 8 subcutaneous injections of placebo or 170 μg LPP administered in increasing doses in 4 visits over 3 weeks. The primary outcome was the combined symptom and medication score (CSMS) measured over the peak pollen season. Reactivity to conjunctival provocation test (CPT) and quality of life (QOL) were assessed as secondary endpoints. RESULTS: The mean reduction in CSMS in the LPP vs. placebo group was -15.5% (p=0.041) during the peak period and -17.9% (p= 0.029) over the entire pollen season. LPP treated group had a reduced reactivity to CPT (p<0.001) and, during the pollen season, a lower rhinoconjunctivitis QOL global score (p=0.005) compared to placebo group. Mostly mild and WAO grade 1 early systemic reaction (ESR) were observed ≤ 30 min in 10.5% of LPP-treated patients, whereas 3 patients with a medical history of asthma (<1%) experienced a serious ESR that resolved with rescue medication. CONCLUSION: LPP administered over 3 weeks before the grass pollen season significantly reduced seasonal symptoms, was generally safe and well-tolerated This article is protected by copyright. All rights reserved.
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