Funded by Dutch Lung Foundation "Longfonds"
Duration: 2017 - 2022
Co-ordinator: Dr. Hermelijn H. Smits, Leiden, NL
Partners: Prof. Pieter S. Hiemstra, Leiden, NL
Prof. Christian Taube, Leiden, NL
Prof. Erika von Mutius, Munich, GE
Prof. Markus Ege, Munich, GE
Prof. Bart Lambrecht, Ghent, BE
Prof. Hamida Hammad, Ghent, BE
Prof. Ben Marsland, Epalinges, CH
Prof. Rick Maizels, Glasgow, UK
Dr. Henry McSorley, Edinburgh, UK


Project Summary:
Asthma is the most common chronic paediatric disorder in Westernized countries. Symptoms
are cough, wheeze, difficulty to breath, and exacerbations in response to viral infections and
allergens. Asthma is characterized by lung inflammation, barrier lining damage and airway
remodelling. There is neither prevention nor cure, only treatments that alleviate symptoms.
Our overarching aim is to mimic nature’s approach of preventing asthma, which has
been deranged by changes in our western life-style.
Protection against asthma is linked to environmental microbial exposure in early life. Examples
are provided by farming, helminth parasites and diet-mediated microbial richness. Farmrelated
protection is independently explained by farm-milk consumption and air-borne
microbial exposure during early life. Chronic helminth infections protect via active immune
regulation of allergic responsiveness, as a side-effect necessary for parasite survival. A rich commensal flora is essential for the maturation of the neonatal immune system. The microbial composition is influenced by our diet and farm-milk may promote its richness. Many studies have pointed out that these microbes can profoundly modify host immune responses at different levels, and in parallel influence the lung barrier and their responsiveness to external triggers.
Asthma is a complex syndrome and we anticipate that not one but rather several prevention strategies might be needed to successfully intervene on a population level. Therefore, we aim to target several pivotal mechanisms to restore crucial interactions between diet, microbiome, immune system and lung barrier in early life. First, we will investigate whether farm-milk protects against asthma in a placebo-controlled intervention study in infants. The preventive role of fiber consumption, farm-dust exposure and recombinant helminth proteins against allergen sensitization and viral respiratory infections will be investigated in (pre-)clinical models. Changes in global gene expression, metabolome and microbiome will be included in both approaches and used to predict which children will benefit most from additional treatments by farm-dust and/or recombinant helminth proteins.
With this multi-pronged approach, we will take a step towards preventing asthma in children. We aim to restore the highly protective and long lasting mechanisms that evolution has developed to avoid overt reactions to allergens and environmental triggers in chronic reactive airway disease.

Funded by German Federal Ministry of Education and Research (BMBF)
Duration: 2017-2021
Coordinator: Prof. Bianca Schaub, Munich, GE
Partners: Prof. Erika von Mutius, Munich, GE
Prof. Wolfgang Greiner, Bielefeld, GE
Prof. Kirsten Beyer, Berlin, GE
Prof. Eckart Hamelmann, Bielefeld, GE
Prof. Michael Kabesch, Regensburg, GE
Prof. Gesine Hansen, Hannover, GE

Project Summary:
The CHAMP Consortium aims to investigate the determinants of different allergic diseases (food allergy, atopic dermatitis, asthma, hay fever) across the whole pediatric age range. Particular attention will be given to factors determining primary tolerance (no onset of disease) and acquired tolerance (remission of existing disease). We will identify clinically relevant biomarkers predicting early onset, progression and remission. As main results, we aim to define a molecular allergy score early in life predicting subsequent allergy risk, to identify predictors of natural tolerance of food allergy and to assess underlying mechanisms in murine models of allergy development with focus on early tolerance induction. We aim to predict mild versus severe allergic diseases, to identify relevant biomarkers and to predict remission of asthma and hay fever. Finally, we expect to HRQoL of patients and quality of life (QoL) of their parents across different allergic diseases, different disease stages and various age groups.
Importantly, this consortium has the unique opportunity to assess the development and remission of childhood allergies at all stages of childhood immune and organ development. In summary, adding novel insight to the puzzle of early onset, natural tolerance and remission of different allergic diseases from birth to adolescence will lay the ground for future development of preventive strategies and shall in the long term contribute to opening up novel avenues for therapeutic options. This will clearly make an impact on the life of our patients and their families.

In terms of disease incidence and mortality, lung diseases are ranked second in the world and are directly or indirectly responsible for every fifth death. The annual cost of lung diseases amounts to 102 billion euros alone for Western Europe. It is expected that the number of patients and thus also the costs will continue to rise in the coming years. To date, there are no cures for most respiratory diseases – just symptomatic treatments. For these reasons it is even more important to conduct research to develop new approaches and options for prevention, diagnosis and therapy. In the German Center for Lung Research (DZL), the leading German research institutes have therefore joined together to combat the most important lung diseases through translational research.

http://www.dzl.de/