In recent years, asthma prevention has been on the forefront of both national and international scientific research. There is increasing evidence that a preventive approach to asthma is possible if we go back to ‘Nature’ and properly educate the immature immune system (the body's natural defence mechanism) in children and strengthen their lung barrier. If we succeed, we will have achieved a significant medical breakthrough.
In recent decades, the number of children suffering from asthma and allergies has strongly increased. The fact that this development coincides with urbanisation and a change in lifestyle has prompted scientists to investigate putative causal links.
Scientists have discovered that some microorganisms have protected us from their harmful cousins for hundred thousands of years. These bacteria and worm parasites are called ‘commensal organisms’. They have been with us from ancient times and play a significant role in how our immune system functions. They affect our lungs, intestinal flora and our immune system. And they prevent severe allergic reactions. Since the start of urbanisation, the number and diversity of these commensal organisms have decreased. The great challenge we face now is to restore the beneficial effects of these original commensals by either rebuilding the original population or by artificially potentiating their pathways of action. The ultimate goal of the scientists of the Asthma Prevention Consortium is the development of a balanced immune system and a protective barrier in the lungs. Sophisticated application of the beneficial properties of commensals should make it possible to prevent the occurrence of asthma in the near future.
The consortium's scope includes five promising subprojects:
Farm milk-based product to prevent asthma
Commensals, microorganisms on and in our body that protect us against their harmful cousins, influence our immune system on a daily basis. The discovery that these important commensals can flourish when children drink raw farm milk has inspired researchers in the design of a product that may prevent asthma.
This product is a baby milk powder made from minimally processed farm milk. The challenge is to produce such a milk powder that is safe for consumption while retaining the preventive properties of the original raw farm milk. The researchers will test its preventive effects in a placebocontrolled randomised intervention trial involving 2700 children. Children will drink the test milk, or normal shop milk as a comparator, from the age of six months up to their third birthday. The researchers will evaluate the frequencies of respiratory tract infections during intervention, and clinical symptoms of allergies and eczema at the age of 3 years, followed by the diagnosis of asthma at the age of 5 years. This extensive and unique trial is a significant challenge for both researchers and young families. It may lead to a major breakthrough!
- Consortium Partner: Ludwig-Maximilians-Universität München
- Research: Clinical trial to investigate the preventive effects of raw farm milk with minimal processing in 2700 babies and toddlers
- Funding requirement: €1.5 million
To predict is to prevent
The researchers involved in the clinical trial (research project 1) estimate that farm milk should be able to prevent asthma in 10 to 15% of children who currently develop asthma. This means thousands of children will then be protected. However, some children may still develop asthma despite the beneficial effects of the minimally processed milk.
The researchers predict that these children may benefit from (additional) treatment with farm dust, worm parasite derivatives and/or a modified diet. Preferably, these children should be identified at an early (st)age before disease has been established. Therefore, the researchers intend to develop a unique diagnostic test, allowing them to pinpoint those children at risk. They will determine which microorganisms can be found in the children over time, which immune-associated genes have become active and which ones have not. As a result, each child will be characterised by its own unique blueprint. This new diagnostic test will be used at a very young age (< 1 year old) to identify which children may benefit from additional treatment(s) in addition to minimally processed farm milk with the aim of reaching full protection against asthma in each child. This personalised approach will allow medical doctors to apply individually-based treatment strategies.
- Consortium Partners: Leiden University Medical Centre, Monash University, LMU Munich
- Research: Development of a diagnostic test to predict which children require (extra) treatment
- Funding requirement: €800,000
Farm dust to fight viruses
Children who grow up on family-run farms suffer significantly less from asthma and allergies compared to children who grow up in urban areas. An equally remarkable fact is that they suffer less from (severe) viral respiratory tract infections during their first year of life. Not only because they often drink farm milk, but also because they inhale the farm dust.
Frequent and severe viral respiratory tract infections during the first year of life increase the risk of developing asthma at a later stage. There are indications that farm dust can protect against these viral infections. The researchers will investigate the mechanism involved in the farm dust-induced protection against viral respiratory tract infections
by for example RS virus and rhinovirus, and thereby against asthma. This knowledge may lead to application of the beneficial effects of farm dust for children in urbanised areas.
- Consortium Partners: Ghent University, Leiden University Medical Center, Essen University Hospital
- Research: Identification of the mechanism behind the protective effects of barnyard dust
- Funding requirement: €1.3 million
Children’s diet against asthma
We know that good nutrition is essential for our health. However, the relationship between specific nutrients and healthy lungs is still largely unknown. Scientists will investigate the production of certain gut-specific molecules by the intestinal flora to gain a better understanding of this relationship.
These specific molecules, known as metabolites, are produced by our intestinal bacteria when we eat a high-fibre diet containing complex sugar structures such as can be found in milk, fruit and vegetables. It is thought that they contribute to a higher tolerance of allergenic particles in the lungs, thereby providing protection against asthma and allergies.
The researchers will investigate whether eating a modified diet may result in unique changes in intestinal flora and metabolite production. And whether or not this plays a key role in protecting against childhood asthma. They will focus on the causal relationship between a special diet and the absence of respiratory tract complaints. This research will point at the beneficial effects of a modified diet that can help to prevent asthma.
- Consortium Partner: Monash University
- Research: The effect of modified diet on intestinal flora and the lungs
- Funding requirement: €1 million
Therapeutic worm molecules
Worm parasites used to be a normal element in our intestinal flora. In tropical countries, various worm parasites are still common. Strikingly enough,
fewer children suffer from asthma in rural areas of those countries and worms may be of influence.
Worm parasites have an inhibitory effect on the human immune system. The parasite has developed a range of mechanisms to ensure its own survival. The researchers intend to use this ‘tool box’ to create a healthy balance in the immune system and prevent it from overreacting to harmless foreign substances. In previous studies, scientists have shown that specific molecules secreted by worms can have a beneficial effect on the immune system and certain tissue cells in the lung. The researchers will synthesise
these worm molecules and test their effectiveness in preventing asthma and inhibiting respiratory tract infections by using mouse models. In addition, the researchers will further identify new ‘therapeutic’ worm molecules that may act in a slightly different way. The ultimate goal is to create a potent cocktail of different molecules, which may target a large variety of immune cells and structural cells in the lung. This fundamental research is the first important step towards testing new and promising therapeutic worm-based approaches in humans.
- Consortium Partners: University of Glasgow, University of Edinburgh, Leiden University Medical Center
- Research: Synthesise and test worm molecules which pacify our immune system and our lungs
- Funding requirement: €1.4 million
The Asthma Prevention Consortium has set itself a target for 2024:
- To have an earmarked product that can protect a significant group of children against asthma and allergies. This product is a milk powder based on minimally processed farm milk. This special milk powder will be an attractive product to be made market-ready.
- To have a predictive diagnostic test showing which children would benefit from additional protection in addition to the special milk powder
- To have an additional preventive treatment based on farm dust, worm parasites and/or nutritional supplements
Patient Advisory Committee
To emphasise the Lung Foundation Netherlands’ commitment to its patient interest agenda a Patient Advisory Committee (PAC) was established for the Asthma Prevention Consortium. The participation of patient representatives affords the consortium direct insight into the issues and challenges faced by children with asthma and their parents/carers. The PAC is responsible for identifying and prioritising topics to be addressed by the consortium from the patient perspective. Their involvement improves outcomes for lung patients and ensures successful implementation of future products.