"Global Allergy Forum" – International think tank on the subject of allergies
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.
Atopic dermatitis is the most widespread chronic inflammatory skin disease. Among allergic disorders, atopic dermatitis is considered to be a model disease. However, in children that are affected, a significant proportion (approx. 40%) experience healing before the onset of adolescence. It is believed that this natural healing is at least partly attributable to as yet undiscovered mechanisms that lead to an immune tolerance of environmental factors like allergens. To date, such mechanisms have not yet been investigated systematically. Research in this area will exert a direct impact on the quality of life of patients.
Divided into six working groups, the participants at the GAF 2015 analysed current problem areas such as environmental factors, particularly their impact on the bacterial flora (microbiota) of the skin, the development and course of atopic diseases, plus prevention strategies.
In the "Psycho-Neuro-Immunological Aspects/Itching" working group, the importance and problems of itching as a primary symptom of atopic dermatitis was a clear-cut subject for elaboration. Compared with pain research, there are major shortcomings in the research undertaken into itching. Itching as a dimension of suffering is not taken seriously by many non-sufferers, nor by society. Progress however can be expected by imaging methods that can visualise the processing of itching by the brain; the same methods have also revealed surprising results about the involvement of hitherto unsuspected regions of the brain in this sensation.
In their investigation of environmental factors, the "Environment/Microbiota" working group looked into outdoor air pollutants but also focused on cutaneous microbiota. Here, a great deal of research work is still undertaken into individual differences, into the actual role of skin surface microbes ("beneficial or harmful") as well as into the potential therapeutic implications of external applications of probiotic bacteria to support anti-inflammatory therapies. Even the relationship between dietary intake, the gastro-intestinal tract and skin microbiota constitutes a new research area.
The "Skin Barrier" working group built on the rapid progress made in recent years; in particular the discovery that, as a result of specific mutations, dryness of the skin and barrier dysfunctionalities can be attributable to genetic factors; (i.e. a mutation in the gene for the epidermal protein filaggrin will lead to a high predisposition to the development of atopic eczema). The group called for further research into an improved and standardised measurement of barrier functions in daily clinical routines as well as intervention studies into correcting malfunctioning barriers (keyword: skin care).
The "Epidemiology and Standardisation" working group turned its attention to epidemiological research methods, where improvements to measuring instruments would lead to a better diagnosis of the disease but also to measurements of the severity of the eczema. The starting point for such investigations should be a database for neurodermatitis at a population level. Such a database does not yet exist. The clear definition of subgroups in the disease as well as an understanding of the roles of prenatal influences and the effects of various intervention programmes appears to be equally important. A need for healthcare research in the field of neurodermatitis appears to be pressing. There is also a lack of basic epidemiological knowledge in the medical profession.
In the "Immune Deviation" working group the importance of immunological but also pharmacological research to correct and remedy aberrant immune responses was underscored. The scope of this critical research also extends to the examination of comorbidities, i.e. the simultaneous emergence of other diseases. New therapeutic approaches also include biologics, i.e. an antibody against the interleukin 4 receptor, as well as inhibitors of kinases and phosphodiesterases. The induction of immunological tolerances to common allergens remains a long-term objective. Encouraging results in allergen-specific immunotherapy (desensitisation) and in neurodermatitis have already been achieved.
A further group addressed the enormous chasm between the scientific progress that has been made in dermatology and allergology and the translation of this knowledge in the everyday work of doctors and the lives of patients. There is a lack of information for key target groups such as physicians, healthcare professionals, patient organisations and, not least, political decision-makers. That's why it is imperative to improve educational activities at all levels and for a multitude of target groups. The aim of the discussions in this working group was to arrive at concepts and actions that would close this information gap.
The results and findings of the 3rd Global Allergy Forum are summarised in the third "Davos Declaration". 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.
Non-allergenic pollen constituents may exacerbate allergies
As part of a study that received significant funding from CK-CARE, scientists at the Helmholtz Zentrum in Munich and the Technische Universität München have discovered a new mechanism that explains how non-allergenic pollen constituents can exacerbate allergies. The so-called B cells play a crucial role in this mechanism. Until now, it has been assumed that the dendritic cells were primarily responsible for any allergy-promoting effects by non-allergenic plant constituents. The newly discovered mechanism relating to B cells therefore presents a new viewpoint on this subject and offers new approaches for the development of therapies in allergic diseases.
"Since the prevalence of pollen constituents may also depend on climatic factors, we, together with the Institute of Biochemical Plant Pathology (BIOP), intend to continue monitoring whether changing climatic conditions are exerting an influence on the B-cell mediated allergenicity of pollen," explains Prof. Claudia Traidl-Hoffmann, Director of CK-CARE.
Mindfulness – new directions in research into itching
The agonizing itching suffered by neurodermatitis patients is a major treatment challenge for both patient and clinician. As well as several other influential factors, stress can also have a negative impact on the course of neurodermatitis. Mindfulness-based stress reduction (MBSR) programmes can demonstrably reduce stress and the consequences of stress. Hence a study initiated by CK-CARE is addressing the question of whether practising mindfulness can have a positive effect on the disease course of neurodermatitis and the itching.
As part of a pilot study, in addition to state-of-the-art dermatological interventions, a classic MBSR programme and neurodermatitis training with elements of mindfulness-based stress reduction were carried out in neurodermatitis patients in the sense of a health-promoting measure. The aim was to study the feasibility (acceptance of the programme, dropout analysis, etc.) and to obtain initial evidence of the effectiveness of both programme components separately and in comparison with each other.
The pilot study was based on a classic pre-post comparison of two mindfulness-based programmes with n = 10 and n = 9 participants. In addition, data were recorded three months after the intervention in terms of a follow-up survey. As well as established measuring instruments in dermatology (SCORAD, DLQI, POEM), two established mindfulness questionnaires (MAAS and FMI) and two instruments for recording stress and strain (PSQ and HADS) were used. Furthermore, open and specific questions were employed in order to assess the benefit and effectiveness of the programmes.
Whereas no significant changes were seen in the dermatological and psychological measurements, the self-assessed attentiveness significantly increased in the first group. In the second group, on the other hand, an increase in inattentiveness was noted, which is a common observation following a systematic mindfulness-based programme. However, the acceptance and subjective rating of the programme as well as the participants’ satisfaction proved very positive.
Mindfulness-based interventions in the sense of health-promoting measures are useful and promising for the symptomatic treatment of itching in terms of generic stress and symptom reduction. The majority of the participants report that the programme helped them to deal better with the symptoms of the illness.
Block course “Allergy in everyday paediatric practice” 2015
“There are lots of good courses – but this is just superb”, was the feedback from people attending the block course.
Not simply because the management of allergies is very central and important in paediatric practice, but also because this CPD for paediatricians in primary care is structured and run in such a way that it is easier for them to incorporate their newly acquired knowledge into everyday practice.
In a collaboration between “Kinderärzte Schweiz” (Swiss Paediatricians) and CK-CARE, the first three courses have successfully been completed, each involving three two-day face-to-face training events and two webinars. A huge thank you to all the highly motivated and actively involved attendees and speakers. We look forward very much to welcoming all participants in courses 4 and 5 as well as more allergy in everyday paediatric practice block courses being planned.
A new treatment for allergies
Scientists from the Swiss Institute of Allergy and Asthma Research (SIAF) in Davos, from the University of Tokyo, the RIKEN Research Institute in Yokohoma, and from Stanford University recently discovered mechanism that stops the body from reacting with an excessive immune reaction. This could be the basis for a new way to handle allergies.
Most people with allergies have to take medication throughout their life: Their body “thinks” that proteins from the environment are so “strange” that they elicit an immune reaction. Until present, it was not possible to develop an efficient therapy so that the body “learns” to stop in an overreacting way.
Mast cells play a key role in the disease process in allergies: As a reaction towards an allergen – for example pollen or dust mites – they release big amounts of substances that initiate an inflammatory process. Study leader Hideaki Morita and his team discovered that mast cells are not only “bad guys”, but also have a “good side” (see figure): They release the substance interleukin-2 that induces the production of certain immune cells called T-regulatory (Treg) cells. Treg cells can suppress the allergic inflammatory process in the airways induced by interleukin-10.
It is already known for some time that Treg cells can subdue an excessive immune response and the resulting inflammation. For example, injections with Treg cells prevented autoimmune diseases in mice. However, for Treg cell treatments one needs a large amount of these cells, which is not easy to realise. In the blood, there are just a few of them, and in vitro they are difficult to produce. Using mast cells, Treg cells could be easily produced in the laboratory in large quantities. “The mechanism that we discovered, could be the basis for a new way to handle allergies," says Hideaki Morita.
Morita et al., An interleukin-33-Mast Cell-interleukin-2 Axis Suppresses Allergic Inflammation Induced by Papain-Promoting Regulatory T Cell Numbers, Immunity (2015), http://dx.doi.org/10.1016/j.immuni .2015.06.021
Change of CK-CARE Board Speaker
At the June meeting of the Board of CK-CARE AG, in line with its rotation policy, the Board advised on who would take up the position of Speaker of CK-CARE. Professor Thomas Bieber (Bonn) was newly nominated, having taken over this office from his predecessor Professor Cezmi Akdis as of 1st July 2015. Professor Peter Schmid-Grendelmeier (Zurich) was elected Deputy Speaker.
Adenosine in ambrosia pollen exacerbates allergy
The common ragweed (Ambrosia artemisiifolia) produces pollen which can trigger strong reactions such as asthma. A research team headed by Prof. Claudia Traidl-Hoffmann, who is on the Board of Directors of CK-CARE (Christine Kühne – Center for Allergy Research and Education), has shown that what was previously known as the principal allergen only has such a strong allergenic effect when combined with the substance adenosine, which is also present in the pollen.
The weed Ambrosia artemisiifolia is an invasive plant from North America, which has two challenging characteristics for humans: it is spreading rapidly in Europe – it is also colonising regions in Switzerland – and its pollen has an allergy-promoting effect even in minute quantities. If ambrosia pollen gets into the airways, it induces severe inflammation in the lung tissue. This can produce breathing problems or even asthma. The main trigger in ambrosia pollen was previously thought to be a protein called “Amb a 1”. A lot of people who have come into contact with ambrosia pollen develop antibodies to this substance. This is basically a protective mechanism of the body against unwanted substances or pathogens, but it is initiated in error when a person has an allergy.
However, the protein Amb a 1 is apparently not solely responsible for the inflammatory effect of the ambrosia pollen, as shown by a team led by Prof. Claudia Traidl-Hoffmann, Director of the Institute of Environmental Medicine at the Technical University of Munich (UNIKA-T, TUM) and member of the Board of Directors of CK-CARE (Christine Kühne – Center for Allergy Research and Education): “This only becomes highly allergenic when in combination with adenosine, which is also contained in ambrosia pollen,” states Prof. Claudia Traidl-Hoffman.
The search for the unknown substance
According to the media release from TUM, the researchers studied how different constituents of the pollen acted on lung tissue. The lung tissue was then tested for indicators of inflammation – such as the presence of specific immune cells. The whole pollen extract or the protein Amb a 1 was tested, while at the same time the pollen extract without proteins was also tested. The results were surprising and revealing, as Prof. Traidl-Hoffmann outlines: “Only the whole extract triggered an allergic effect, making it clear that another substance must be causing the allergenic action of the pollen as well as the protein Amb a 1.”
Adenosine was considered as an interesting candidate for substance X. The researchers had already detected it in high concentrations in birch pollen and it is also present in large quantities in ambrosia pollen. They hit the bull’s eye with this theory: once adenosine had been removed from the whole pollen extract, only very slight signs of inflammation occurred. Similarly, if adenosine was administered alone, no pronounced allergic reaction was observed in the lungs. This means: “Only the combination of substances causes an allergic reaction,” concludes Prof. Claudia Traidl-Hoffman.
Will we soon have a possible remedy for allergic asthma?
An interesting aspect is that adenosine is found naturally in the human body. It is involved in lots of processes and nearly all cells carry recognition molecules for adenosine on their surface. So how does adenosine actually intensify an allergic reaction? “Pollen adenosine binds to the endogenous receptors and, in combination with other substances, can trigger allergies”, explains Prof. Claudia Traidl-Hoffman. The research group calls this phenomenon “cross-kingdom signalling”, in which plant messengers bind to human receptors.
The results of the study are also promising with regard to treatment. So-called adenosine receptor antagonists are drugs that can help to treat asthma by blocking the adenosine receptors in the body. Therefore this aspect is also important in terms of research into pollen allergy. “The results show that adenosine plays a key role, especially in the exacerbation of an allergic reaction. This means the inflammatory reaction could be inhibited by blocking the adenosine receptors, where possible”, states the doctor and researcher.
M. Wimmer, F. Alessandrini, S. Gilles, U. Frank, S. Oeder, M. Hauser, J. Ring, F. Ferreira, D. Ernst, J. B. Winkler, P. Schmitt-Kopplin, C. Ohnmacht, H. Behrendt, C. Schmidt-Weber, C. Traidl-Hoffmann, J. Gutermuth, Pollen-derived adenosine is a necessary cofactor for ragweed allergy, Allergy, May 2015.
Children, allergy, diet and environment
Around 30% of children suffer from allergies nowadays. These often start with so-called “childhood eczema”– neurodermatitis – as early as infancy. The symptoms of allergy sometimes disappear, but sometimes the condition deteriorates and additional symptoms occur, i.e. hay fever, asthma and food allergies may develop.
What prevents an allergy from developing in childhood?
This key question is being addressed in a CK-CARE research project. Why does our immune system develop a misdirected inflammatory reaction to harmless substances that surround us every day and actually do us no harm? Our modern lifestyle certainly encourages allergy development – that much is known. Our diet, the move away from an agricultural way of life, excessive hygiene, the use of pharmaceuticals, etc., all combine as contributory factors. However, diet in very early childhood plays a crucial role in whether or not a person develops an allergy, as discovered by CK-CARE – and other research teams worldwide. Hence the digestive has a decisive part to play. As knowledge in this field is still very limited, CK-CARE is conducting what is known as an observational study on the development of allergy in childhood.
Children are being observed from newborn infants up to 3 years of age: this includes keeping a “food diary”, investigating the environmental conditions and regularly checking the children for allergy symptoms. Microbial colonisation of skin, throat and bowel is identified and the function of the immune cells in the body is analysed. Breath tests are carried out and breastmilk is tested. The completed questionnaires are scanned, the data are exported, then transferred in anonymised form to the central CK-CARE study database.
Targeted laboratory testing of substances that might suppress allergies
Based on early research work, it was possible to treat allergies with short-chain fatty acids (e.g. ingredients of butter). In collaboration with the SIAF, Davos, the team has now investigated in the laboratory whether treatment as early as pregnancy might be helpful. In addition, experiments are being conducted to study a potential effect of these fatty acids on inflammation of the bowel.
Precise and timely pollen forecast thanks to new automated pollen sampler
One in seven people living in Germany, which means about 12 million people in total, suffers from symptoms of pollen allergies ranging from allergic rhinitis through hay fever to anaphylactic shocks. The symptoms appear with the beginning of the flowering season of the respective allergenic plants. That is why allergic patients are dependent on daily updated information about pollen dispersal in order to precisely adjust their medication and plan possible outdoor activities.
The pollen exposure in the city of Augsburg is subject of a CK-CARE research project which takes place at the University Centre for Health Sciences (UNIKA-T). The results from this research project should provide a more detailed view of local pollen allergen exposure. Its chief aim is to enable doctors and allergic patients to use preventive and therapeutic treatments in the best possible way.
Since the beginning of April 2015, pollen exposure has been measured by means of the BAA500 automatic pollen sampler from the company Hund, which is installed at the Bavarian Environment State Agency (LfU) adjacent to the University of Augsburg. This sampler draws in the surrounding air and afterwards counts the pollen contained therein with a precision of over 90 percent.
Until now, airborne pollen have been measured with conventional pollen traps. These traps draw in the surrounding air and fix the pollen contained therein on an adhesive tape. The corresponding tapes are prepared by hand after the sampling. Following this, the pollen have to be counted manually under an optical microscope. This process is time consuming and must only be performed by trained staff. Due to the time consuming tape preparation and the ensuing counting, relevant data can be provided within one day after the sampling at the earliest, though normally within ten days. Therefore, when using the conventional traps, any pollen forecast has to be built upon data that is several days old.
The new automated pollen sampler provides relevant data within three hours after the sampling took place and the resulting forecasts are considerably more adequate.
Caroline Roduit awarded the “Müller-Preis”
The Board of the Allergy Foundation Ulrich Müller-Gierok has recognized paediatrician Dr. Caroline Roduit (staff member of WP4) with this year Müller Award for her interesting and clinically important publication about food allergy in children.
Prof. Peter Schmid-Grendelmeier new SSAI President
At this year’s general meeting of the Swiss Society for Allergology and Immunology (SGAI) in Basel, Peter Schmid-Grendelmeier was appointed the society’s new President. He will hold this office for two years from 2015 to 2017.
Peter Schmid-Grendelmeier has already been active on the SSAI board for several years, for instance as former chairman of the SSAI Specialist Commission and in recent years as the liaison person with aha! Swiss Allergy Centre.
The Swiss Society for Allergology and Immunology (SSAI), founded in 1950, is also a widely recognized organisation in the field of allergology and immunology at the international level, with nearly 600 members and a variety of conferences. The aims of the SSAI are to encourage an exchange of information between basic researchers and doctors in clinical practice, to promote training and continuing education opportunities in the area of allergology and immunology and to contribute towards good treatment of patients suffering from these diseases.
Davos Research Institute moves into Hochgebirgs-Campus
The research base at Davos is consolidating. The well-known Institut für Allergieforschung (Institute for Allergy Research) is moving into the Hochgebirgsklinik.
Davos. – The Davos Hochgebirgsklinik was successfully saved from bankruptcy and wants to restructure itself as an allergy research and clinical campus with an international reputation. This project is being supported by the renowned Swiss Institute for Allergie and Asthma Research (SIAF).
In a policy decision, the foundation governing body of this research institute based in Davos has unanimously supported the SIAF relocation to the Hochgebirgsklinik site.
Project with worldwide resonance
On Wednesday the SIAF announced that this decision means it will be supporting the creation of a “Hochgebirgs-Campus Davos” for patient-oriented allergology teaching and research. As a consequence, the Hochgebirgsklinik is one large and significant step closer to its goal of creating a world-leading centre for translational medicine where clinical practice and research work together under one roof.
Based on initial, rough planning, the move by SIAF with around 50 staff is expected to happen by mid-2016. (béz)
Datum: 11.09.2014, 06:30 Uhr
CK-CARE Allergy Education Week 2015
The second ALLERGY EDUCATION WEEK will take place once again in Davos, Switzerland, from September 7 to 13, 2015. This will include the Summer School, featuring the topic "Allergy and the Brain".