Blowing into a tube to diagnose asthma is not easy for babies or toddlers.
Babies and young children suspected of having asthma therefore inevitably remain without a clear diagnosis until around the age of five.
According to Alexander Möller, senior consultant in pneumology at the University Children’s Hospital Zurich (Kispi), this creates a risk that these children will not receive the correct treatment.
“If their asthma remains untreated, there is a high risk of more frequent and severe asthma attacks, and the chronic inflammation can lead to scarring that restricts lung function,” Möller said.
“If, on the other hand, the children do not have asthma but, for example, bronchitis, yet are still given asthma medication, this can in some circumstances lead to significant side effects, such as for example, stunted growth.”
Previous research into asthma has shown the complex composition of the air reflects the inflammatory changes associated with asthma in the lungs. It has already been proven that asthma has a strong genetic component. Empa, (the Swiss Federal Laboratories for Materials Science and Technology) and Kispi now intend to build on these findings in a joint research project. Empa’s Multi-Omics for Healthcare Materials research team, led by Marija Buljan, has expertise in statistical analysis and the molecular mechanisms underlying disease development, while Alexander Möller’s research group at Kispi contributes breath analysis and clinical experience.
The project is based on a multi-omics approach, which investigates the development and severity of asthma at various molecular and genetic levels. The aim of the project is to develop a novel diagnostic protocol that enables non-invasive and pain-free asthma diagnosis, even in babies and young children. This protocol is to consist of two components: a buccal swab for DNA analysis and a breath analysis using mass spectrometry.
The teams have planned the research project to run for four years and have divided it into five phases. The first two phases aim to identify molecules typical of asthma in exhaled air and assess whether these can support a diagnosis. To this end, Kispi is recruiting 180 children aged between two and four for a prospective longitudinal observational study, comprising 120 with recurrent respiratory symptoms and 60 healthy children for the control group. These children breathe into a special bag so that their exhaled air can be analysed in a specialised instrument, a high-resolution time-of-flight mass spectrometer. To identify and classify the specific molecules within the vast amounts of data generated, Kispi researchers have developed a machine learning model. Based on the findings, they predict whether the children will later be diagnosed with asthma.
“Once they reach the age of five, we verify this prediction using the established diagnostic protocol,” Möller said.
The later phases will focus on identifying genetic variants associated with asthma, with the aim of creating a gene panel. This would be a cost-effective method to support the diagnosis of asthma.
“Once a gene panel is in place, there is no need to examine the entire genome; instead, can specifically search for the presence of certain asthma-associated gene variants in a patient,” Buljan said.
To identify these genetic variants, the Empa researchers are developing a computer model that maps cellular signalling pathways. The focus is on specific immune cells that are involved in triggering symptoms in the vast majority of children with asthma.
“The map of cellular signalling pathways shows us which messenger substances lead to the activation of these cells and what changes occur in the cells following contact with the messenger substances,” Buljan said.
To validate that they have identified the correct cellular processes, the researchers then conduct laboratory experiments with the cells, thereby identifying the genes that play a central role.
The goal is to compile a definitive list of asthma gene variants. A mouth swab is taken from a dozen parent-child pairs who have already been diagnosed with asthma, which the researchers use to check whether these gene variants are present. The gene panel is ultimately created based on these results.
If the research project proves successful, it would solve a huge problem worldwide.
“That would be a quantum leap for paediatric pulmonology,” Möller said.
“With an early diagnosis, we could largely relieve affected toddlers of their asthmatic symptoms and prevent hospital admissions. At the same time, it would minimise the risk of non-asthmatic children being unnecessarily prescribed cortisone. A better understanding of the cellular mechanisms underlying asthma could serve as a basis for developing targeted and well-tolerated medications,” Buljan said.
The first priority, however, is to successfully complete the project on early asthma diagnosis. It is expected to take another five to 10 years before the new diagnostic protocol is finalised and established in paediatric medicine.