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 dieases- just symptomatic treatments.

Asthma is the most prevalent chronic respiratory disease in childhood and is also very common in adults. Although the clinical manifestations of asthma in children and adults are rather uniform with wheezing, shortness of breath and cough, population-based clinical and genetic studies suggest that asthma is not one disease, but many. Thus, a single “one-size-fits-all” treatment approach is unlikely to work to tackle this important health problem. In order to design personalized treatment approaches for asthma patients, there is urgent need to elucidate the mechanisms underlying the various types of asthma. The decoding of such mechanisms and their translation to the individual patient is the aim of the Disease Area Asthma and Allergy of the DZL and their clinical flagship project ALLIANCE (All Age Asthma Cohort).

The CHAMP Consortium investigates 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 examine 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. Furthermore/ we will analyse HRQoL of patients and quality of life (QoL) of their parents across different allergic diseases, different disease stages and various age groups.

This consortium has the unique opportunity to assess the development and remission of childhood allergies at all stages of childhood immune and organ development. Adding new 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. In the long term, this shall contribute to open up novel avenues for therapeutic options. This clearly will make an impact on the life of our patients and their families.

This project aims to disentangle the role of inflammatory regulation (NF-κB and MAPK signalling) during immune maturation in childhood asthma development and its protection via environmental stimulation. Having blood samples from several time points of two birth cohorts and one cross-sectional cohort of children, which are at risk for asthma or protected from asthma offers a unique opportunity to examine immune mechanisms of asthma development. Two central mechanisms of interest are pro- and anti-inflammatory pathways during immune maturation and how these can be modulated in order to prevent the development of childhood asthma.

Multinational study on rural environmental protection for childhood asthma – a central role for dendritic and regulatory B-cells during immune maturation

This multinational study aims to identify central mechanisms of environmental protection for childhood asthma in both Europe and China. By assessing dendritic cells (DC) and regulatory B-cells (Breg) during immune maturation, this project aims to disentangle novel central regulatory hubs which contribute to asthma protection via two strong asthma-protective environments.

The unique chance of having consecutive blood samples of children at several ages of an European birth cohort from the strongest asthma-protective environment, namely farming, available and in parallel recruiting Chinese children from urban HongKong (and Guangzhou) with high asthma prevalence and rural Conghua with low prevalence at age 6 years allows the comparison of asthma-protective mechanisms across Europe and China.

This project aims to disentangle distinct protective immune regulatory mechanisms of A20-mediated effects of dendritic (DC) and regulatory T cells (Tregs) for childhood asthma by stimulation of blood cells with compounds of environmentally distinct areas. The unique natural exposure to two environments strongly protecting from childhood asthma, i.e. farms in Europe and rural areas in China offers the great opportunity to assess underlying immune mechanisms which are distinct from each other.

As A20 (anti-inflammatory) and inflammasome regulation have been shown differentially expressed following different dust stimulation, we will identify the specific role of A20 and inflammasome regulation following environmental exposure with different dusts in cell lines, and isolated cells. We will disentangle specific asthma-protective immune mechanisms via A20-mediated effects of DCs on Tregs through exposure to distinct rural environmental dust in healthy and asthmatic children. We will unravel the effect of environmental dust extracts from different environmental areas (Germany, Finland, China) on T reg-function, methylation, acetylation (FOXP3 promoter), and mTOR signalling. We aim to identify signalling of A20 regulation in DCs and inflammasome activation. We aim to investigate the effect of A20-regulation in DCs and inflammasome activation on Treg-mediated suppression. Finally, in a proof-of-principle experiment, we will assess the effects of dust stimulation on A20-regulation in DCs, inflammasome and Treg regulation in children protected from asthma in comparison to asthmatic children. 

The EFRAIM project prospectively investigated protective factors in early life influencing the development of allergies in birth cohorts conducted in rural areas in five European countries. Detailed information on a great variety of environmental exposures was collected and large biobanks have been established. The mechanisms mediating these protective exposures such as the maturation of immune responses, gut colonisation, the mucosal barrier function and the genetic and epigenetic factors interacting with the environmental exposures were investigated.

Currently, allergic diseases can be managed effectively but not cured. The knowledge about protective exposures early in life can, however, be turned into the development of preventive strategies. The EFRAIM project was expected to produce ground-breaking new insights on protective agents and their mechanisms that can be used to prevent the further development of allergies.

In 2019, the 16 year follow-up of the cohort is starting. 

Paulina/Paulchen are two prospective birth cohorts that have been recruited since 2008 and 2009 in Munich and in a rural area in the Munich area. Here, the risk and protection against asthma in the populations can be examined. The aim is to investigate the influence of early risk factors or protective factors on the immune system and the development of asthma and allergies in childhood. This implements, among other things, the study of genetics, epigenetics and gene expression. The children are now older than 16 years and are continuously tracked for the development of asthma and allergies.

The Clara/Claus study is a large cross-sectional study on bronchial asthma in Munich. The aim of the study is to investigate immune regulation in the development of bronchial asthma in childhood. A detailed questionnaire is collected, the children are clinically characterized in detail and the immune system is examined at various levels (genetics, epigenetics, gene regulation, cytokines) and the microbiome is recorded. The children will be followed up after 1 and 3 years. The results should help to define different asthma phenotypes, to better understand their pathophysiology and to identify new mechanisms of disease development.

The recent publication by Beerweiler et al. in Allergy (2024) has attracted significant media attention.

Please find below links related to “The Secret of Barn Dust” and “How Barn Dust Protects Against Asthma”. 

Note: The following links are in German:

Health!: How Barn Dust Protects Against Asthma and Other Allergies – [Watch here]

Asthma: Symptoms and Treatment | NDR.de – Guide – Health

Country Life: Why Barn Dust Can Reduce Allergic Asthma | tagesschau.de 

Original publication: Farm-dust mediated protection of childhood asthma: Mass cytometry reveals novel cellular regulation

Claudia Carina Beerweiler, Michael Salvermoser, Johanna Theodorou, Andreas Böck, Franziska Sattler, Paulina Kulig, Vinko Tosevski, Bianca Schaub | Allergy. 2024 Nov;79(11):3022-3035. doi: 10.1111/all.16347. Epub 2024 Oct 14. https://doi.org/10.1111/all.16347

“Yes, we care” - this was the motto of an online information event of the ALLIANCE (All Age Asthma Cohort) asthma study. More than 70 people, many of them study participants their family members, joined in. All ALLIANCE study centers of the German Center for Lung Research (DZL) invited patients to get information on research results and to start a dialog with science.

"Twelve years after the start of the study, ALLIANCE would like to report on a potpourri of important scientific successes and findings," said Dr. Nicole Maison from Dr. von Hauner Children's Hospital of Ludwig-Maximilians University Clinic Munich, welcoming the participants. She helped organize the online event and guided through the program. However, it was not intended to be a one-sided monologue from ALLIANCE doctors and scientists to patients: "In the future, we want to involve our patients even more in our research and give them the opportunity to address their wishes and questions to us researchers," said Maison.

In the first lecture, "The colorful picture of asthma - what types of asthma are there and how do they progress?", Dr. Isabell Ricklefs (University Medical Center Schleswig-Holstein, Lübeck) gave a vivid insight into the different types of asthma and presented exciting research data. "We want our patients to understand why we perform so many examinations on them, such as lung function tests, nasal swabs and blood samples, which are not always pleasant, especially for our youngest participants," Dr. Ricklefs explained, "and what an important role this plays for our research."

Dr. Tobias Trojan (University Hospital of Cologne) and Prof. Christine Happle (Hannover Medical School) reported on the significance of obesity for the development and progression of asthma. “The fact that obesity of mother and child can have an influence even before birth is an important finding from our ALLIANCE research,” Trojan and Happle said.

In her empathetic contribution entitled “Asthma from a patient's perspective”, Kimberley Schlieter, a medical student from Lübeck and patient herself, built a direct bridge between the patients and the researchers of the ALLIANCE study. She sees herself as a link and part of the team and is happy to be available to the participants and researchers in her role as a patients’ representative.

In a lively discussion, ALLIANCE scientists answered questions about future research projects, such as the use of artificial intelligence. It became emotional when a patient explained that she was proud to be able to make a contribution to asthma research and thus might make asthma more bearable for future generations. The researchers also expressed their joy and gratitude for the collaboration with the participants and their relatives.

In the end, it was clear that patients, relatives and scientists all benefit from the resulting dialog. This is to be continued in a series of events in the coming years.

ALLIANCE is a flagship project of the DZL that has so far recruited more than 1,000 people between the ages of six months and 84 years and is studying their disease progression at follow-up visits. The aim is to understand the mechanisms of disease progression and to identify them better and earlier so that treatment can be adapted to individual patients.

Learn more

4th DZL period has started in January 2024 (-2027):

The Disease Area Asthma and allergy with the Munich CPC-M scientific coordinators Bianca Schaub and Nicole Maison (as young academy) together with Susanne Krauss-Etschman (Borstel) has the following major goals:

For the ALL Age Asthma Cohort (ALLIANCE):

1. to identify mechanisms resulting in early loss of function and asthma progression and compare findings across DAs;

2. to continue the follow-up of successfully recruited ALLIANCE patients with a focus on the ‘comorbidome’ and aging;

3. to increasingly integrate patient perspective into ALLIANCE research;

For basic research:

4. to address trained/mistrained immunity for asthma development & protection,

5. to study microbes providing a health- or asthma-promoting environment,

6. to investigate ung function loss and resilience,

7. to foster biomarker development for diagnostic improvement, and

8. to identify synthetic and natural compounds for prevention and therapy.

https://dzl.de/krankheitsbereiche/asthma-und-allergien/

The 11th DZL annual meeting took place in Fürstenfeldbruck from June 14th to 16th. It was organized by the DZL Munich location (CPC-M). More than 550 researchers gathered here to exchange knowledge and promote collaboration in the field of lung research.

A great success for the DZL Munich location was the election of Prof. Dr. med Schaub and Dr. Nicole Maison as scientific coordinator and DZL Academy Fellow coordinator of the disease area “AA”.

https://www.cpc-munich.de/en/newsevents/news/news/article/31081.html

Prof. Dr. med. Bianca Schaub was awarded a professorship of LMU Munich (Heisenberg Professorship of DFG, german research foundation) with the title “Environment and development of immunological tolerance” („Umwelt und immunologische Toleranzentwicklung“) with the focus on the development of allergic diseases. This was now succesfully prolonged. The Heisenberg Professorship, named after the physicist, promotes excellent scientists following criteria of scientific excellence

New Publication by Johanna Krusche, MonikaTwardziok, Katharin Rehbach...Bianca Schaub in Journal of Allergy and Clinical Immunology about TNF-α–induced protein (link).

Kristina Laubhahn (Phd Student at the group of Prof. Dr. med. Bianca Schaub) has been awarded an oral abstract prize for an outstanding oral abstract presentation at the EAACI 2019 conference.
The title was: Pathway analysis - genetic and immunological influences of gene polymorphisms in 17q21 locus on childhood wheeze.

Prof. Dr. med. Bianca Schaub was awarded a professorship of LMU Munich (Heisenberg Professorship of DFG, german research foundation) with the title “Environment and development of immunological tolerance” („Umwelt und immunologische Toleranzentwicklung“) with the focus on the development of allergic diseases. The Heisenberg Professorship, named after the physicist, promotes excellent scientists following criteria of scientific excellence.

Prof. Schaub, Consultant and Deputy Head of the Department of Allergology in the University Children´s Hospital of Munich, Dr. von Hauner Children's Hospital, examines the role of early life immune maturation for the development of allergic disease since numerous years.

The focus of this Heisenberg Professorship comprises the assessment of the environment and the development of immunological tolerance from birth until allergy development in childhood. This will be investigated in several birth and cross-sectional cohorts of children with risk or protection from allergies. To characterize molecular mechanisms of the different phenotypes, a number of methods of „computational medicine“ will be used. The identification of biomarkers for specific therapy strategies for childhood allergic diseases will contribute to develop future prevention studies and clinicial studies with novel biologicals.