| 1. |
- Diamant, Zuzana, et al.
(författare)
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Toward clinically applicable biomarkers for asthma : An EAACI position paper
- 2019
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 74:10, s. 1835-1851
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation, structural, and functional abnormalities within the airways are key features of asthma. Although these processes are well documented, their expression varies across the heterogeneous spectrum of asthma. Type 2 inflammatory responses are characterized by increased levels of eosinophils, FeNO, and type 2 cytokines in blood and/or airways. Presently, type 2 asthma is the best-defined endotype, typically found in patients with allergic asthma, but surprisingly also in nonallergic patients with (severe) asthma. The etiology of asthma with non-type 2 inflammation is less clear. During the past decade, targeted therapies, including biologicals and small molecules, have been increasingly integrated into treatment strategies of severe asthma. These treatments block specific inflammatory pathways or single mediators. Single or composite biomarkers help to identify patients who will benefit from these treatments. So far, only a few inflammatory biomarkers have been validated for clinical application. The European Academy of Allergy & Clinical Immunology Task Force on Biomarkers in Asthma was initiated to review different biomarker sampling methods and to investigate clinical applicability of new and existing inflammatory biomarkers (point-of-care) to support diagnosis, targeted treatment, and monitoring of severe asthma. Subsequently, we discuss existing and novel targeted therapies for asthma as well as applicable biomarkers.
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| 2. |
- Kappen, Jasper, et al.
(författare)
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Standardization of clinical outcomes used in allergen immunotherapy in allergic asthma : An EAACI position paper
- 2023
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Ingår i: Allergy: European Journal of Allergy and Clinical Immunology. - 0105-4538. ; 78:11, s. 2835-2850
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In allergic asthma patients, one of the more common phenotypes might benefit from allergen immunotherapy (AIT) as add-on intervention to pharmacological treatment. AIT is a treatment with disease-modifying modalities, the evidence for efficacy is based on controlled clinical trials following standardized endpoint measures. However, so far there is a lack of a consensus for asthma endpoints in AIT trials. The aim of a task force (TF) of the European Academy of Allergy and Clinical Immunology (EAACI) is evaluating several outcome measures for AIT in allergic asthma. Methods: The following domains of outcome measures in asthmatic patients have been evaluated for this position paper (PP): (i) exacerbation rate, (ii) lung function, (iii) ICS withdrawal, (iv) symptoms and rescue medication use, (v) questionnaires (PROMS), (vi) bronchial/nasal provocation, (vii) allergen exposure chambers (AEC) and (viii) biomarkers. Results: Exacerbation rate can be used as a reliable objective primary outcome; however, there is limited evidence due to different definitions of exacerbation. The time after ICS withdrawal to first exacerbation is considered a primary outcome measure. Besides, the advantages and disadvantages and clinical implications of further domains of asthma endpoints in AIT trials are elaborated in this PP. Conclusion: This EAACI-PP aims to highlight important aspects of current asthma measures by critically evaluating their applicability for controlled trials of AIT.
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| 3. |
- Oefner, Carolin M., et al.
(författare)
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Tolerance induction with T cell-dependent protein antigens induces regulatory sialylated IgGs
- 2012
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 1097-6825 .- 0091-6749. ; 129:6, s. 1647-1647
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Tidskriftsartikel (refereegranskat)abstract
- Background: Under inflammatory conditions, T cell-dependent (TD) protein antigens induce proinflammatory T-and B-cell responses. In contrast, tolerance induction by TD antigens without costimulation triggers the development of regulatory T cells. Under both conditions, IgG antibodies are generated, but whether they have different immunoregulatory functions remains elusive. Objective: It was shown recently that proinflammatory or anti-inflammatory effector functions of IgG molecules are determined by different Fc N-linked glycosylation patterns. We sought to examine the Fc glycosylation and anti-inflammatory quality of IgG molecules formed on TD tolerance induction. Methods: We administered chicken ovalbumin (OVA) with or without costimulus to mice and analyzed OVA-reactive IgG Fc glycosylation. The anti-inflammatory function of differentially glycosylated anti-OVA IgGs was further investigated in studies with dendritic cell cultures and in an in vivo model of allergic airway disease. Additionally, we analyzed the Fc glycosylation pattern of birch pollen-reactive serum IgGs after successful allergen-specific immunotherapy in patients. Results: Stimulation with TD antigens under inflammatory conditions induces plasma cells expressing low levels of alpha 2,6-sialyltransferase and producing desialylated IgGs. In contrast, plasma cells induced on tolerance induction did not downregulate alpha 2,6-sialyltransferase expression and secreted immunosuppressive sialylated IgGs that were sufficient to block antigen-specific T- and B-cell responses, dendritic cell maturation, and allergic airway inflammation. Importantly, successful specific immunotherapy in allergic patients also induced sialylated allergen-specific IgGs. Conclusions: Our data show a novel antigen-specific immunoregulatory mechanism mediated by anti-inflammatory sialylated IgGs that are formed on TD tolerance induction. These findings might help to develop novel antigen-specific therapies for the treatment of allergy and autoimmunity. (J Allergy Clin Immunol 2012;129:1647-55.)
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| 4. |
- Papadopoulos, Nikolaos G, et al.
(författare)
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Research needs in allergy: an EAACI position paper, in collaboration with EFA.
- 2012
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Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century.The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels.Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein.
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