New asthma therapy at Hochgebirgsklinik Davos
The Hochgebirgsklinik Davos, as a partner of the Allergy Campos Davos, treats allergic diseases as a priority. Davos offers a healthy climate and the air is low in allergens and pollutants.
Asthma is a complex, highly heterogeneous disease with various phenotypes of respiratory inflammation. Since June 2016 injections of an interleukin-5 antibody instead of cortisone have been given in Switzerland to patients with very severe eosinophilic asthma. The concept of anti-IL-5 treatment has proved clinically beneficial in asthma with severe eosinophilic airway inflammation.
The treatment received its licence in Switzerland in June 2016 and, in special cases of severe bronchial asthma, can markedly improve the symptoms and reduce the exacerbation rate (asthma attacks). On 11 August 2016 a patient with severe eosinophilic asthma was the first to be injected with an interleukin-5 antibody (mepolizumab) at the Hochgebirgsklinik Davos. IL-5 is a cytokine which plays an important role in the development, activation, differentiation and survival of eosinophils.
After the decision to treat and application by a lung specialist, the treatment costs for mepolizumab (Nucala) are met by the cost bearers for patients with a specific subgroup of difficult-to-treat bronchial asthma (“eosinophilic asthma”).
Prof. Hans-Werner Duchna would be very happy to provide you with detailed information about this treatment. On request, the medical service of HGK will support you in the application process or the formalities of obtaining confirmation of insurance coverage.
Cellular and molecular immunological process in neurodermatitis patients
On the occasion of the third Global Allergy Forum Davos, the CK-CARE directors together with a group of internationally leading researchers from the field of allergic skin diseases, compiled an article which concentrates particularly on innovative developments in neurodermatitis and was recently published in the Journal of Allergy & Clinical Immunology. The journal dedicated the cover page of that edition to the subject of neurodermatitis (picture; Werfel et al., 2016: 138: 336-349).
The article tackles the following topics: skin barrier in neurodermatitis, neurodermatitis subgroups, personalised medicine, microbiomes, changes in the immune response, allergen-specific IgE antibodies, mechanisms of itching, allergens and other environmental factors and diagnosis and treatment.
There is a considerable, unmet medical need to define immunological endotypes of neurodermatitis because these have significant repercussions for the forthcoming stratification of the phenotype of neurodermatitis and the resulting, targeted therapies in the development of personalised medicine. Studies on novel biological agents, which have been used in the treatment of neurodermatitis, are also presented in this review. The clinical efficacy of new immunological approaches using biological agents in patients with neurodermatitis is proved by the use of dupilumap (an antibody that blocks recognition of IL-4). A number of studies with other pharmaceuticals that specifically target the immune system players are currently underway. Such approaches might have immunomodulatory and hence positive clinical effects on the general condition of the skin, as well as on the underlying immune discrepancy, which play a role in concurrent diseases. The effect of these immunological treatments on the disturbed microbiome in neurodermatitis patients and in itching might yield other potentially positive knowledge of use for treatment purposes.
Davos shows support for planned Allergy Campus
With a clear lead of 83%, the Davos voters are behind the planned Allergy Campus Davos on the site of the Hochgebirgsklinik.
Full article "Davoser Zeitung" (in German only)
Report on the 7th CK-CARE Team Meeting in 2016
As they do every year, members of the CK-CARE Consortium met in the Davos Congress Centre in September 2016. The meeting was attended by more than 50 participants and a highlight of the research year.
Thomas Bieber (Speaker of CK-CARE) at the 2016 CK-CARE Team Meeting
As well as individual reports from the Work Packages and different locations, the focus was primarily on an exchange of experiences and further training. The latter was achieved by organising three workshops with the key topics of “Microbiome”, “Scientific writing” and “Statistics and study design”. All the participants were able to attend all three workshops on a rotation basis and hence benefit from the latest developments in these three selected areas.
Before the dinner in the Restaurant Spina, team members enjoyed a fascinating and entertaining speech by Professor Ring from Munich, who gave the attendees a deep insight into the mysteries of allergy from his perspective and with his special brand of humour. Finally, on a torch-lit walk back from the restaurant, the group was able to reflect again on the many memorable experiences gained in the team meeting.
The annual team meeting is and remains an important element of the scientific exchange, but also the team spirit that exists within the CK-CARE research consortium.
Pollen monitoring online
On 13 September 2016, the Bavarian Cabinet approved the setting up of the world’s first automatic pollen monitoring network (ePIN) as part of the “Bayern Digital” initiative (Press Release 253, Bavarian State Chancellery). The initiative, jointly supported by the two ministries of “Environment and Consumer Protection” (StMUV) and “Health and Care Services” (StMGP), is based on preliminary studies by the Centre for Allergy and Environment (ZAUM) of the Technical University of Munich, a partner of CK-CARE.
The network involves several innovations:
- In a pilot study, a maximum network of 27 pollen monitors was set up in Bavaria and operated for a year. These established which locations are sufficient and necessary for determining the pollen count in Bavaria. As Bavaria, can be subdivided into eight pollen count regions, eight stations are sufficient for reliable measuring. This meant that the cost and complexity of pollen monitoring could be reduced.
- In a three-year experiment, the suitability of an automated pollen monitor was compared with that of the classic manual method (microscopy). The error rate was equally high but of a different character for the two methods. The greatest error for the automated method was that not all pollens were recognized (if they varied from the classic external appearance) and were consequently classified as “unknown”. As a result of repeated use of the system, the recognition software will automatically improve over time. By contrast, the manual systems have already been optimised and cannot be further improved.
The new system will be set up from 2017 to 2018 and should be running continuously from 2019. Similar efforts are being made in Switzerland, but this favour using the monitor from a Swiss company.
The system has enormous advantages for patients: the pathogens causing the common disease of pollen allergy or “hay fever” (over 80% of allergy sufferers are allergic to pollen) are visualised on line with this system and give patients the opportunity to react specifically to the triggers of their condition, especially since the system allows far more accurate pollen forecasts to be made than in the past.
Fig. 1. (A) Prof. Dr. Jeroen Buters (ZAUM) with an automatic pollen monitor (BA500 from Hund in Wetzlar, Germany) and
B) the planned pollen monitoring network in Bavaria, a combination of manual pollen traps (historical stations, blue) and new, automatic pollen monitors (red).
Jeroen Buters 1,2
1 ZAUM – Centre for Allergy & Environment, Helmholtzzentrum Munich/Munich Technical University
2 CK-CARE, Christine Kühne – Center for Allergy Research and Education, Davos
Paul Ehrlich Award to Cezmi Akdis
The Paul Ehrlich Award 2016 for Improving Experimental Research is awarded to Professor Dr Cezmi Akdis, MD. Cezmi Akdis is the Director of the Swiss Institute of Allergy and Asthma Research (SIAF), Davos, and Professor in the Zurich University Medical Faculty, as well as being one of the Directors of the Christine Kühne Center for Allergy Research and Education (CK-CARE) in Davos.
2015 Annual Report of CK-CARE
Again in 2015 CK-CARE can report successful activities and important results that also have an impact on allergy sufferers. For instance, considerable progress has been made in terms of measuring allergy triggers and environmental influences.
The barrier function of the skin, which is central to protecting against allergy triggers, has been further understood and in studies has been improved in a therapeutically effective way. CK-CARE identified factors that enable at-risk children to be identified and promptly protected against developing allergies. Furthermore, food ingredients were discovered which have a preventive effect and may be used in future to prevent allergies. The education of medical primary care providers, as the second major pillar of CK-CARE activities along with research, has been further expanded and continually improved by thorough evaluation. In 2015 the Global Allergy Forum was held for the third time with great success.
Read more about the work in the CK-CARE research groups and the activities in CK-CARE Education in the past year.
Identification of new effector B cell subgroups and their role in allergic diseases
B cells play an important role in the human immune system because they are the cells that produce antibodies. A research team at SIAF led by Professor Cezmi Akdis (Workpackage 2) recently reported that B cells – apart from their role antibody-producing cells – can function as regulators of the immune response by the production of cytokines. Certain subgroups of B cells were identified which produce specific cytokines. For instance, regulatory B cells produce the anti-inflammatory cytokine interleukin-10 and are hence able to protect against autoimmune diseases and allergic inflammation.
The aim of this study is to identify new human cytokine-producing B cell subgroups and research their role in immune regulation. B cells cannot be cultured for lengthy periods in vitro. Therefore we suppressed the cell division of the B cells by increasing the production of two specific genes (BCL-6 and BCL-xL). The method of suppressing cell division and increasing the production of certain proteins is known as over-expression. This makes it possible for us to form long-lived B cells. To enable us to characterise individual B cells, we isolated individual cells and generated B cell clones. Then we studied the gene activity of these clones in detail by means of next-generation sequencing (determining the nucleotide sequence of the RNA).
Identification of cytokine-producing B cell subgroups.
The RNA expression of 32 identical B cell clones was measured by means of next-generation sequencing. 6 clone clusters produce similar cytokines. Thus B cell clones in each cluster can have different specific functions for regulation of the immune response
To allow us to identify new effector B cell subtypes that produce specific cytokines, we had to group the individual B cell clones based on their cytokine expression. Using this approach we identified 6 clone groups which expressed specific cytokine profiles, i.e. activated specific cytokines. Some of these cytokine profiles (an expression profile shows what the cell actually does) resembled previously described subgroups of effector B cells, such as the interferon-gamma-producing B cells and the interleukin-10-producing regulatory B cells. Interferon is a protein that exerts an immunostimulating, primarily antiviral effect; interleukin is a cytokine with an anti-inflammatory effect, which inhibits the inflammatory reactions taking place in the body. In addition, we found other clusters with different cytokine profiles, which have not previously been described. At present we are working on carrying out detailed characterisation of these new B cell subgroups so that their potential role in allergic diseases can be assessed.
“Scientific Allergy” magazine – No. 3/2016
With “Scientific Allergy” CK-CARE provides themed issues of the magazine in a loose sequence. These present current findings from allergy research for primary care providers in general practice and paediatric practice. However, “Scientific Allergy” may also be displayed in practices to provide information for patients.
In issue No. 3 you will find, among other items, practical tips on the right course of action in “Anaphylaxis – how to detect anaphylaxis quickly and react correctly” and articles on subjects such as “Allergy prevention – how you can advise parents”, “Allergen-specific immunotherapy – when is ‘hypersensitization’ advisable?”.
It is our declared aim to increase knowledge about allergic diseases. We feel sure that “Scientific Allergy” will inspire people to engage intensely with allergic diseases and utilise advances in research for the benefit of allergy sufferers.
In vivo study proves: low-molecular, non-allergenic pollen compounds enhance the allergen-specific immune response in humans
A scientific team led by Dr. Stefanie Gilles, Dr. Isabelle Beck and Professor Claudia Traidl-Hoffmann (Member of the Board of Directors and Coordinator in Workpackage 1 of CK-CARE) from the university Department of Environmental Medicine, demonstrated in vivo the clinical relevance of low-molecular pollen compounds with the aid of skin prick tests and nasal provocation tests.
The researchers tested effects of allergens from birch and grass pollen with and without the addition of low-molecular pollen compounds
During the course of the study, skin prick tests and nasal provocation tests were performed on healthy and allergic subjects. Allergens from birch and grass pollen were used for the tests. The pollen allergens were prepared for testing either in a saline solution or with a low-molecular fraction of the pollen extract. The skin prick tests then produced a stronger allergic immune reaction (wheals, redness) when the low-molecular pollen fraction was added. In the nasal provocation tests, the low-molecular pollen compounds increased the local release of interleukin-8 (IL-8) and immunoglobulin E (IgE). Increased production of nasal discharge was observed in the study group in which the low-molecular pollen fraction was added. More severe runny nose and itchy eyes, an increased urge to sneeze and other intensified symptoms were also observed. Healthy subjects did not react measurably to the pollen compounds in the study neither in prick tests on the skin nor in nasal provocation tests.
Close-up nasal epithelium
The results of the study might alter allergy diagnostics and allergen-specific immunotherapy
With this pilot study, the research team led by Gilles has done crucial groundwork for future clinical trials, which should investigate in more depth the effects of low-molecular, non-allergenic compounds from pollen. Non-allergenic compounds might be of clinical relevance, especially in allergy diagnostics and in allergen-specific immunotherapy (“hyposensitization”) because pollen extracts are currently being used in these areas. Whether these extracts currently in use contain pro-inflammatory substances and in what quantities has not yet been adequately investigated.
The publication entitled “Pollen derived low molecular compounds enhance the human allergen specific immune response in vivo”, which appeared on 04.2016 in the journal Clinical and Experimental Allergy, will therefore be significant for future clinical research in the allergy field.
Davos Declaration No 3
Instigated by CK-CARE (Christine Kühne – Centre for Allergy Research and Education), the Global Allergy Forum has now been held in Davos for the third time. From 28 June until 1 July, some 70 world-renowned scientists in the field of allergology and its allied disciplines convened to discuss challenges and possible solutions in the field of atopic dermatitis/eczema.
The results and findings are summarised in the third "Davos Declaration" and published in the journal 'Allergy'. It reflects the current state of research, education, healthcare and knowledge transfer, as well as put forward concrete proposals for improving the situation in allergology.
Successful interdisciplinary cooperation between microbiology and allergology – from field research to cutting edge molecular biology
Pollen has a specific microbiome for every plant species!
The number and severity of diseases based on pollen allergies is constantly increasing. Scientists now assume that plants’ own defence mechanisms against environmental factors, such as exhaust fumes or adverse microbial overload, bear a significant share of the allergenicity of pollen and pollen-associated compounds. It is important to understand that microbes in themselves do not have a negative impact on plants (and people). Instead, the “right mix” (diversity) of microbes appears to be crucial to the health of human, animal and environment. The publication quoted below first describes the different types and number of microbes to be found on birch and grass pollen. The differences in the pollen microbiome between different species of plant are described as well as the differences between the pollen microbiome of the same plant species, but under the influence of different environmental factors such as location and pollution burden. In a second step, possible correlations between air pollution, pollen microbiome and the allergenicity of pollen were established.
Close-up birch pollen
If we damage the environment less, the allergenicity of plant pollen will also decrease
In this connection the research team established that precisely air pollution (traffic load) and a “harmful microbial load” have a negative influence on the allergenicity of pollen – hence more allergen is released. The aim now is to understand what induces pollen to release more allergen and what microbes act as trigger factors in this process. It seems clear that allergen production and allergen release are a defensive reaction – a type of stress situation that is intended to ensure the plant’s survival. A more positive influence on the plant world is needed in future through sustainable management of the environment, so that plants produce less (disease-causing) pollen allergen and hence patients have fewer symptoms and fewer allergies arise.
In February 2016, for the field of medicine, the relevant publication “Pollen-Associated Microbiome Correlates with Pollution Parameters and the Allergenicity of Pollen“ (first author: Andrea Obersteiner) was successfully published in the internationally highly-ranked specialist journal PLOS One. The publication is the result of excellent interdisciplinary cooperation between the Institute for Environmental Medicine at UNIKA-T and the Department of Microbe-Plant Interaction at the Helmholtz Centre in Munich. The scientific colleagues at the Institute for Environmental Medicine, Stefanie Gilles, Isabelle Beck and Franziska Häring, and the Institute Director Claudia Traidl-Hoffmann are pleased that, through their research efforts, they have made a unique contribution to the understanding of the connection between microbiome, air pollution and the allergenicity of pollen.