Allergen-specific immunotherapy of Hymenoptera venom allergy:also a matter of diagnosis

Stings of hymenoptera can induce IgE-mediated hypersensitivity reactions in venom-allergic patients, ranging from local up to severe systemic reactions and even fatal anaphylaxis. Allergic patients' quality of life can be mainly improved by altering their immune response to tolerate the venoms by injecting increasing venom doses over years. This venom-specific immunotherapy is highly effective and well tolerated. However, component-resolved information about the venoms has increased in the last years. This knowledge is not only able to improve diagnostics as basis for an accurate therapy, but was additionally used to create tools which enable the analysis of therapeutic venom extracts on a molecular level. Therefore, during the last decade the detailed knowledge of the allergen composition of hymenoptera venoms has substantially improved diagnosis and therapy of venom allergy. This review focuses on state of the art diagnostic and therapeutic options as well as on novel directions trying to improve therapy

Prioritizing research challenges and funding for allergy and asthma and the need for translational research-The European Strategic Forum on Allergic Diseases

The European Academy of Allergy and Clinical Immunology (EAACI) organized the first European Strategic Forum on Allergic Diseases and Asthma. The main aim was to bring together all relevant stakeholders and decision-makers in the field of allergy, asthma and clinical Immunology around an open debate on contemporary challenges and potential solutions for the next decade. The Strategic Forum was an upscaling of the EAACI White Paper aiming to integrate the Academy's output with the perspective offered by EAACI's partners. This collaboration is fundamental for adapting and integrating allergy and asthma care into the context of real-world problems. The Strategic Forum on Allergic Diseases brought together all partners who have the drive and the influence to make positive change: national and international societies, patients' organizations, regulatory bodies and industry representatives. An open debate with a special focus on drug development and biomedical engineering, big data and information technology and allergic diseases and asthma in the context of environmental health concluded that connecting science with the transformation of care and a joint agreement between all partners on priorities and needs are essential to ensure a better management of allergic diseases and asthma in the advent of precision medicine together with global access to innovative and affordable diagnostics and therapeutics.Peer reviewe

Prioritizing Research Challenges and Funding for Allergy and Asthma and the Need for Translational Research : The European Strategic Forum on Allergic Diseases

The European Academy of Allergy and Clinical Immunology (EAACI) organized the first European Strategic Forum on Allergic Diseases and Asthma. The main aim was to bring together all relevant stakeholders and decision-makers in the field of allergy, asthma and clinical Immunology around an open debate on contemporary challenges and potential solutions for the next decade. The Strategic Forum was an upscaling of the EAACI White Paper aiming to integrate the Academy's output with the perspective offered by EAACI's partners. This collaboration is fundamental for adapting and integrating allergy and asthma care into the context of real-world problems. The Strategic Forum on Allergic Diseases brought together all partners who have the drive and the influence to make positive change: national and international societies, patients' organizations, regulatory bodies and industry representatives. An open debate with a special focus on drug development and biomedical engineering, big data and information technology and allergic diseases and asthma in the context of environmental health concluded that connecting science with the transformation of care and a joint agreement between all partners on priorities and needs are essential to ensure a better management of allergic diseases and asthma in the advent of precision medicine together with global access to innovative and affordable diagnostics and therapeutics.Peer reviewe

A Direct Performance Test for Assessing Activities of Daily Living in Patients with Mild Degenerative Dementia: The Development of the ETAM and Preliminary Results

Background: There are currently only a few performance tests that assess the capacity to perform activities of daily living. These measures frequently require a long time to administer, are strongly cognition oriented, or have not been adequately validated. Methods: The Erlangen Test of Activities of Daily Living in Mild Dementia (ETAM) was developed in a 4-phase process that was based on the International Classification of Functioning, Disability, and Health (ICF). A pilot study was conducted on 30 subjects with mild dementia with a mean age of 80 years. The subjects' mean score on the MMSE was 21.5. Twenty-one of the 30 subjects were women. Results: Ten items were developed and tested in the pilot study. The mean time required to complete the test was 26 min. The item analysis showed difficulties that ranged primarily from r = 0.28 to r = 0.79. The ETAM had a moderate correlation with the MMSE (rMMSE = 0.310) and a low correlation with the Geriatric Depression Scale-15 (GDS-15; rGDS-15 = 0.149). Conclusion: The preliminary version of the ETAM is quick and easy to use and has predominantly satisfactory item characteristics. There still is the need to revise the items ‘giving directions' and ‘making tea' with regard to standardisation

A Direct Performance Test for Assessing Activities of Daily Living in Patients with Mild Degenerative Dementia: The Development of the ETAM and Preliminary Results

Background: There are currently only a few performance tests that assess the capacity to perform activities of daily living. These measures frequently require a long time to administer, are strongly cognition oriented, or have not been adequately validated. Methods: The Erlangen Test of Activities of Daily Living in Mild Dementia (ETAM) was developed in a 4-phase process that was based on the International Classification of Functioning, Disability, and Health (ICF). A pilot study was conducted on 30 subjects with mild dementia with a mean age of 80 years. The subjects' mean score on the MMSE was 21.5. Twenty-one of the 30 subjects were women. Results: Ten items were developed and tested in the pilot study. The mean time required to complete the test was 26 min. The item analysis showed difficulties that ranged primarily from r = 0.28 to r = 0.79. The ETAM had a moderate correlation with the MMSE (rMMSE = 0.310) and a low correlation with the Geriatric Depression Scale-15 (GDS-15; rGDS-15 = 0.149). Conclusion: The preliminary version of the ETAM is quick and easy to use and has predominantly satisfactory item characteristics. There still is the need to revise the items ‘giving directions' and ‘making tea' with regard to standardisation

Validation of the Erlangen Test of Activities of Daily Living in Persons with Mild Dementia or Mild Cognitive Impairment (ETAM)

Background: There are currently no valid, fast, and easy-to-administer performance tests that are designed to assess the capacities to perform activities of daily living in persons with mild dementia and mild cognitive impairment (MCI). However, such measures are urgently needed for determining individual support needs as well as the efficacy of interventions. The aim of the present study was therefore to validate the Erlangen Test of Activities of Daily Living in Persons with Mild Dementia and Mild Cognitive Impairment (ETAM), a performance test that is based on the International Classification of Functioning and Health (ICF), which assesses the relevant domains of living in older adults with MCI and mild dementia who live independently. Methods: The 10 ICF-based items on the research version of the ETAM were tested in a final sample of 81 persons with MCI or mild dementia. The items were selected for the final version in accordance with 6 criteria: 1) all domains must be represented and have equal weight, 2) all items must load on the same factor, 3) item difficulties and item discriminatory powers, 4) convergent validity (Bayer Activities of Daily Living Scale [B-ADL]) and discriminant validity (Mini Mental State Examination [MMSE], Geriatric Depression Scale 15 [GDS-15]), 5) inter-rater reliabilities of the individual items, 6) as little material as possible. Retest reliability was also examined. Cohen's ds were calculated to determine the magnitudes of the differences in ETAM scores between participants diagnosed with different grades of severity of cognitive impairment. Results: The final version of the ETAM consists of 6 items that cover the five ICF domains communication, mobility, self-care, domestic life (assessed by two 3-point items), and major life areas (specifically, the economic life sub-category) and load on a single factor. The maximum achievable score is 30 points (6 points per domain). The average administration time was 35 min, 19 of which were needed for pure item performance. The internal consistency was α =.71. The three-week test-retest reliability was r =.78, and the inter-rater reliability was r =.97. The ETAM also provided satisfactory discrimination between healthy individuals and persons with MCI or mild dementia as well as between persons with mild and moderate dementia. Conclusions: The 6-item final version of the ETAM shows satisfactory psychometric characteristics and can be administered quickly. It is therefore suitable for use in both clinical practice and research

Additional file 2: of Validation of the Erlangen Test of Activities of Daily Living in Persons with Mild Dementia or Mild Cognitive Impairment (ETAM)

ETAM evaluation and documentation form. (DOC 82 kb

A mutually beneficial collaboration between the European Academy of Allergy and Clinical Immunology Junior Members and Clinical and Translational Allergy

International audienceThe European Academy of Allergy and Clinical Immunology (EAACI) Junior Members (JM) comprise the largest EAACI section with around 4000 clinicians and scientists under 35 years of age working in the field of allergy and clinical immunology. The Junior Member collaboration with Clinical and Translational Allergy Journal is a mutually beneficial relationship providing Junior Members of EAACI with excellent opportunities to publish their work in the Journal, enhance their visibility in their respective field, and get involved with Journal-related activities and processes. In the future, this collaboration will grow, not only by the consolidation of these activities, but also by the implementation of new initiatives, such as a platform for discussing and/or publishing Junior Members' dissertations in the Journal. From the CTA perspective, the collaboration presents an opportunity to promote a new generation of allergists with experience of conducting and presenting research, with improved skills in critical review

Improved efficacy of allergen-specific immunotherapy by JAK inhibition in a murine model of allergic asthma.

Allergen-specific immunotherapy (AIT) is the only curative treatment for type-1 allergies, but sometimes shows limited therapeutic response as well as local and systemic side effects. Limited control of local inflammation and patient symptoms hampers its widespread use in severe allergic asthma.Our aim was to evaluate whether AIT is more effective in suppression of local inflammation if performed under the umbrella of short-term non-specific immunomodulation using a small molecule inhibitor of JAK pathways.In C57BL/6J mice, a model of ovalbumin (OVA)-induced allergic airway inflammation and allergen-specific immunotherapy was combined with the administration of Tofacitinib (TOFA, a FDA-approved JAK inhibitor) from 48 hours prior to 48 hours after therapeutic OVA-injection. The effect of TOFA on human FOXP3+CD4+ T cells was studied in vitro.AIT combined with short-term TOFA administration was significantly more effective in suppressing total cell and eosinophil infiltration into the lung, local cytokine production including IL-1β and CXCL1 and showed a trend for the reduction of IL-4, IL-13, TNF-α and IL-6 compared to AIT alone. Furthermore, TOFA co-administration significantly reduced systemic IL-6, IL-1β and OVA-specific IgE levels and induced IgG1 to the same extent as AIT alone. Additionally, TOFA enhanced the induction of human FOXP3+CD4+ T cells.This proof of concept study shows that JAK inhibition did not inhibit tolerance induction, but improved experimental AIT at the level of local inflammation. The improved control of local inflammation might extend the use of AIT in more severe conditions such as polyallergy, asthma and high-risk patients suffering from mastocytosis or anaphylaxis

Dogmas, challenges, and promises in phase III allergen immunotherapy studies

The concept of treatment of an allergy with the offending allergen was introduced more than a century ago. Allergen immunotherapy (AIT) is the only disease modifying treatment of allergic diseases caused by inhalational allergens and insect venoms. Despite this, only few AIT products have reached licensure in the US or an official marketing authorization status in European countries. Moreover, most of these AIT products are provided on an individual patient basis as named patient products (NPP) in Europe, while individualized preparations of (mixed) allergenic extract vials for subcutaneous administration (compounding) is common practice in the US. AIT products are generally considered safe and well tolerated, but the major practical clinical development challenge is to define the optimal dose and prove the efficacy and safety of these products using state-of-the art Phase II and pivotal Phase III studies. In planning Phase II-III AIT studies, a thorough understanding of the study challenges is essential (e.g. variability and non-validated status of subjective primary endpoints, limitations of pollen season definitions) and dogmas of these products (e.g., for sublingual immunotherapy (SLIT) trials double-blinding conditions cannot be maintained, resulting in stronger placebo responses in the active treatment group and inflated treatment effects in Phase III). There is future promise for more objective biomarker endpoints (e.g. basophil activation (CD63 and CD203c), subsets of regulatory dendritic, T and B cells, IL-10-producing group 2 innate lymphoid cells; alone or in combination) to overcome several of these dogmas and challenges; innovation in AIT clinical trials can only progress with integral biomarker research to complement the traditional endpoints in Phase II-III clinical development. The aim of this paper is to provide an overview of these dogmas, challenges and recommendations based on published data, to facilitate the design of Phase III studies and improve the evidence basis of safe and effective AIT products. Keywords: Allergen immunotherapy; Biomarker; Blinding; Phase III; Placebo effect