Final Report Summary - FORALLVENT (Forum for allergy prevention)
The prevalence of asthma and allergies across Europe is very high. About one in ten children suffers from asthma, a fourth of the population is affected by hay fever and about a third reveals a positive allergy test. Numbers for adults are even higher when work place exposures are also taken into account. The associated societal burden of costs for the treatment and management of these conditions is enormous. There is urgent need in health care for novel and innovative approaches to find avenues for the prevention and cure of allergic diseases. Current therapies are effective in controlling symptoms in most patients, but no curative or preventive approach has been found. In the last decades, there has been an accumulation of data not only on the epidemiological aspects of allergic diseases but also on specific risk and protective factors that govern the differential development of allergic diseases in rural and urban areas of Europe. Epidemiological observations suggest that strong protective factors are found in populations with a rural life style and with contact to farm animals.
Children raised in these environments have lower rates of sensitisation to environmental allergens than children growing up in rural environments but without exposure to farm characteristics. If it were possible to understand the precise nature of these 'farm factors' and the underlying immunological mechanisms, then we may be able to exploit the findings for preventive and therapeutic interventions. The overall aim of the FORALLVENT project had been to create a platform and forum for the development of strategies enabling to close the gap between the science on allergic diseases and the practical application of its results in prevention, clinical treatment and the formulation of specialised foods.
As a first step in the FORALLVENT project, a comprehensive review on the literature discussing protective environmental exposures related to the hygiene hypothesis was compiled. Furthermore, a synoptic report highlighting the gaps in existing knowledge was written. In this second report, particular attention was given to identify gaps in existing knowledge and to propose future directions of work. Both reports are posted on the FORALLVENt website (please see http://www.forallvent.info/Achievements online).
In April 2007, the first interdisciplinary symposium 'Environmental, genetic and immunological determinants of allergic and autoimmune diseases' was held in Basel, Switzerland. There is evidence to suggest that the 'hygiene hypothesis' may not only apply to allergic illnesses but also to autoimmune disorders. Therefore, world experts in the field of allergy and autoimmune diseases such as diabetes type 1, rheumatoid arthritis, multiple sclerosis and inflammatory bowel diseases were brought together to discuss similarities and differences in the application of the 'hygiene hypothesis' in their respective fields of research. The summary of the meeting is posted on the FORALLVENT website (please see http://www.forallvent.info /Media Corner/Press kit/Conference Proceedings online).
The first immunology workshop in February 2008 summarised the current state of knowledge about the immune system and its function in the development of allergic conditions. The presentations and discussions from this workshop were summarised in a report. One session of this workshop discussed recent findings from experimental studies. Inhalation of stable dust extracts by mice during sensitisation to ovalbumin was shown to inhibit the development of airway hyperresponsiveness and airway eosinophilia upon challenge. Stable dust extracts also redirected human dendritic cells away from The immune responses. These findings support the notion that stable dust from animal farms contains strong immuno-stimulating substances. Further discussions during this workshop related to the interplay of cells and mediators of the innate and adaptive immune response, including dendritic cells and regulatory T cells; the importance of gene-by-environment-interactions and gene expression studies as markers of cell activation and signal transduction; and the mechanisms underlying the protective effect of consumption of raw cow's milk or raw milk cheese in the gastrointestinal mucosa.
The second workshop was held in January 2009 at the Leiden University Medical Center, Netherlands. The focus of the workshop was to link epidemiological findings with potentially underlying mechanisms and to discuss the many emerging gaps in knowledge. The first session related to gut immunology. How are signals from the gut lumen transcribed into systemic immune responses controlling inflammatory reactions of other organs? The fact that despite a rich microflora with potentially strong inflammatory molecules, the gut is not in a constant state of inflammation indicates that strong anti inflammatory responses are at place guarding the integrity of the mucosa. The question whether a change in gut microflora can lead to the disruption of local tolerance must be addressed. The notion that food ingredients, i.e. vitamin A metabolites may play an important role in the balance between pro and anti inflammatory immune responses was discussed. By identifying and applying specific nutritional compounds, for example those in 'farm milk', the production of 'healthy foods' induce tolerance may be possible. A considerable number of industrial companies had been invited. Many of them declared great interest in the subject and in future collaboration, although most of them were unable to attend the workshop. A resulting position paper discussing the potential avenues into innovative prevention strategies was delivered (please see http://www.forallvent.info/Achievements online).
Experts from the fields of allergology, immunology, epidemiology, food science, food technology, nutrition and communication met to exchange background knowledge and to discuss the potential for an intervention study to assess the allergy preventive effect of 'farm milk'. The application of milk in an intervention study requires above all a safe product. The possibility of producing a safe unpasteurised cow's milk was explored from all perspectives. The fact that the present laboratory technologies do not allow bacterial analyses of raw milk in a timely manner to discard contaminated samples and that dormant, damaged or non-viable microbes cannot be detected, prohibits the use of unpasteurized milk for study purposes.
The FORALLVENT project provided resources for the follow up of the PASTURE cohort beyond age 1. Losses to follow up have been minimised through regular contact to the study participants. Information about activities of the study centres was provided for the participants by locally developed newsletters in each country and through local websites. The health status and the environmental exposure of the study participants have been assessed by parental interviews in yearly intervals in all study centres (Germany, Austria, Switzerland, Finland and France). The follow up questionnaires at age 3, 4 and 5 were drafted as part of the FORALLVENT project. As the recruitment period of the cohort expanded over 2.5 years, the participants are not all of the same age. Therefore, while the interviews at age 3 have been finalised, questionnaire assessment at age 4 and 5 is still ongoing and 4.5 year old children are being appointed for clinical examination. Results of the blood tests were sent to the participating families. A full clinical assessment will be necessary at age 6 years to assess the development of asthma and atopy among study subjects with sufficient certainty. Detailed standard operating procedure protocols (SOPs) for the clinical evaluation of asthma and allergies including allergy testing, lung function testing, skin examination and blood sampling for genomic, proteomic and peptidomic analyses have been drafted.
The FORALLVENT project ended in a final symposium in January 2009 entitled 'The hygiene hypothesis, new insights into allergic and autoimmune diseases'. Top scientist from all over Europe came together in the magnificent Leopoldinum Hall of the University of Wroclaw, Poland to present latest insights on the role of the 'Hygiene hypothesis' in the discussion about the epidemiology of allergic and autoimmune diseases in Europe and the Western World. Representatives from industry, physicians and scientists from all parts of Europe and media representatives mainly from Poland took great interest in the event. Poland was chosen to host the symposium as a bridge between Eastern and Western Europe. Abstracts of the presentations are available on the FORALLVENT website (please see http://www.forallvent.info/Media Corner/Press kit/Conference Proceedings online). After the symposium several articles were published in public and professional newspapers and magazines in Poland and several TV interviews were broadcasted on national and local Polish TV stations.
Ecos communication had been enlisted as partner in charge for professional dissemination of achievements in the FORALLVENT project to the broad public, to the scientific community, to potential industrial partners and to patient organizations. All FORALLVENT events in year 2009 were published on the CORDIS website. The project website http://www.forallvent.info has become the main communication channel. It has regularly been updated. The website will remain active for at least five years after the end of the project. It gives information about the FORALLVENT partners and links to related websites. All workshop and conference results - as far as not confidential - have been published on the project website. It has been created to be informative to professionals, but also to the public. This strategy proved to be successful. Several other websites are referring now to pages published on http://www.forallvent.info. At the end of the project a handy standard brochure in English was produced, which addresses to opinion leaders, decision makers, scientists and the interested public. It covers the main topics and questions of the project and lists of addresses to obtain further information. It can be downloaded from the FORALLVENT website (please see http://www.forallvent.info/Media Corner/Press kit/Press kit 2009 online). A highly motivated and extraordinarily cooperative group of outstanding European experts in various allergy and immunology related fields formed over the duration of the FORALLVENT project. This group includes not only partners in FORALLVENT and partners in the PASTURE cohort study, but also opinion leaders from related scientific groups, from related industrial branches and from the media, who have been inspired by the FORALLVENT idea.
Children raised in these environments have lower rates of sensitisation to environmental allergens than children growing up in rural environments but without exposure to farm characteristics. If it were possible to understand the precise nature of these 'farm factors' and the underlying immunological mechanisms, then we may be able to exploit the findings for preventive and therapeutic interventions. The overall aim of the FORALLVENT project had been to create a platform and forum for the development of strategies enabling to close the gap between the science on allergic diseases and the practical application of its results in prevention, clinical treatment and the formulation of specialised foods.
As a first step in the FORALLVENT project, a comprehensive review on the literature discussing protective environmental exposures related to the hygiene hypothesis was compiled. Furthermore, a synoptic report highlighting the gaps in existing knowledge was written. In this second report, particular attention was given to identify gaps in existing knowledge and to propose future directions of work. Both reports are posted on the FORALLVENt website (please see http://www.forallvent.info/Achievements online).
In April 2007, the first interdisciplinary symposium 'Environmental, genetic and immunological determinants of allergic and autoimmune diseases' was held in Basel, Switzerland. There is evidence to suggest that the 'hygiene hypothesis' may not only apply to allergic illnesses but also to autoimmune disorders. Therefore, world experts in the field of allergy and autoimmune diseases such as diabetes type 1, rheumatoid arthritis, multiple sclerosis and inflammatory bowel diseases were brought together to discuss similarities and differences in the application of the 'hygiene hypothesis' in their respective fields of research. The summary of the meeting is posted on the FORALLVENT website (please see http://www.forallvent.info /Media Corner/Press kit/Conference Proceedings online).
The first immunology workshop in February 2008 summarised the current state of knowledge about the immune system and its function in the development of allergic conditions. The presentations and discussions from this workshop were summarised in a report. One session of this workshop discussed recent findings from experimental studies. Inhalation of stable dust extracts by mice during sensitisation to ovalbumin was shown to inhibit the development of airway hyperresponsiveness and airway eosinophilia upon challenge. Stable dust extracts also redirected human dendritic cells away from The immune responses. These findings support the notion that stable dust from animal farms contains strong immuno-stimulating substances. Further discussions during this workshop related to the interplay of cells and mediators of the innate and adaptive immune response, including dendritic cells and regulatory T cells; the importance of gene-by-environment-interactions and gene expression studies as markers of cell activation and signal transduction; and the mechanisms underlying the protective effect of consumption of raw cow's milk or raw milk cheese in the gastrointestinal mucosa.
The second workshop was held in January 2009 at the Leiden University Medical Center, Netherlands. The focus of the workshop was to link epidemiological findings with potentially underlying mechanisms and to discuss the many emerging gaps in knowledge. The first session related to gut immunology. How are signals from the gut lumen transcribed into systemic immune responses controlling inflammatory reactions of other organs? The fact that despite a rich microflora with potentially strong inflammatory molecules, the gut is not in a constant state of inflammation indicates that strong anti inflammatory responses are at place guarding the integrity of the mucosa. The question whether a change in gut microflora can lead to the disruption of local tolerance must be addressed. The notion that food ingredients, i.e. vitamin A metabolites may play an important role in the balance between pro and anti inflammatory immune responses was discussed. By identifying and applying specific nutritional compounds, for example those in 'farm milk', the production of 'healthy foods' induce tolerance may be possible. A considerable number of industrial companies had been invited. Many of them declared great interest in the subject and in future collaboration, although most of them were unable to attend the workshop. A resulting position paper discussing the potential avenues into innovative prevention strategies was delivered (please see http://www.forallvent.info/Achievements online).
Experts from the fields of allergology, immunology, epidemiology, food science, food technology, nutrition and communication met to exchange background knowledge and to discuss the potential for an intervention study to assess the allergy preventive effect of 'farm milk'. The application of milk in an intervention study requires above all a safe product. The possibility of producing a safe unpasteurised cow's milk was explored from all perspectives. The fact that the present laboratory technologies do not allow bacterial analyses of raw milk in a timely manner to discard contaminated samples and that dormant, damaged or non-viable microbes cannot be detected, prohibits the use of unpasteurized milk for study purposes.
The FORALLVENT project provided resources for the follow up of the PASTURE cohort beyond age 1. Losses to follow up have been minimised through regular contact to the study participants. Information about activities of the study centres was provided for the participants by locally developed newsletters in each country and through local websites. The health status and the environmental exposure of the study participants have been assessed by parental interviews in yearly intervals in all study centres (Germany, Austria, Switzerland, Finland and France). The follow up questionnaires at age 3, 4 and 5 were drafted as part of the FORALLVENT project. As the recruitment period of the cohort expanded over 2.5 years, the participants are not all of the same age. Therefore, while the interviews at age 3 have been finalised, questionnaire assessment at age 4 and 5 is still ongoing and 4.5 year old children are being appointed for clinical examination. Results of the blood tests were sent to the participating families. A full clinical assessment will be necessary at age 6 years to assess the development of asthma and atopy among study subjects with sufficient certainty. Detailed standard operating procedure protocols (SOPs) for the clinical evaluation of asthma and allergies including allergy testing, lung function testing, skin examination and blood sampling for genomic, proteomic and peptidomic analyses have been drafted.
The FORALLVENT project ended in a final symposium in January 2009 entitled 'The hygiene hypothesis, new insights into allergic and autoimmune diseases'. Top scientist from all over Europe came together in the magnificent Leopoldinum Hall of the University of Wroclaw, Poland to present latest insights on the role of the 'Hygiene hypothesis' in the discussion about the epidemiology of allergic and autoimmune diseases in Europe and the Western World. Representatives from industry, physicians and scientists from all parts of Europe and media representatives mainly from Poland took great interest in the event. Poland was chosen to host the symposium as a bridge between Eastern and Western Europe. Abstracts of the presentations are available on the FORALLVENT website (please see http://www.forallvent.info/Media Corner/Press kit/Conference Proceedings online). After the symposium several articles were published in public and professional newspapers and magazines in Poland and several TV interviews were broadcasted on national and local Polish TV stations.
Ecos communication had been enlisted as partner in charge for professional dissemination of achievements in the FORALLVENT project to the broad public, to the scientific community, to potential industrial partners and to patient organizations. All FORALLVENT events in year 2009 were published on the CORDIS website. The project website http://www.forallvent.info has become the main communication channel. It has regularly been updated. The website will remain active for at least five years after the end of the project. It gives information about the FORALLVENT partners and links to related websites. All workshop and conference results - as far as not confidential - have been published on the project website. It has been created to be informative to professionals, but also to the public. This strategy proved to be successful. Several other websites are referring now to pages published on http://www.forallvent.info. At the end of the project a handy standard brochure in English was produced, which addresses to opinion leaders, decision makers, scientists and the interested public. It covers the main topics and questions of the project and lists of addresses to obtain further information. It can be downloaded from the FORALLVENT website (please see http://www.forallvent.info/Media Corner/Press kit/Press kit 2009 online). A highly motivated and extraordinarily cooperative group of outstanding European experts in various allergy and immunology related fields formed over the duration of the FORALLVENT project. This group includes not only partners in FORALLVENT and partners in the PASTURE cohort study, but also opinion leaders from related scientific groups, from related industrial branches and from the media, who have been inspired by the FORALLVENT idea.
