Researchers are developing a noninvasive diagnostic protocol using breath analysis and cheek swabs to identify asthma before age 5.
RT’s Three Key Takeaways:
- Diagnostic Limitations: Children younger than 5 years old typically cannot complete standard lung function tests, leaving young patients without a clear diagnosis and at risk for improper clinical management.
- Multi-Omics Approach: A joint Swiss study combines mass spectrometry breath analysis and buccal swab genetic screening to identify molecular and genetic markers of pediatric asthma painlessly.
- Clinical Potential: Accurate early identification could curb severe exacerbations, prevent permanent airway remodeling, and eliminate unnecessary corticosteroid exposure in children with nonasthmatic respiratory illnesses.
Children are usually unable to perform the lung function tests required for an asthma diagnosis until they reach 5 years of age, leaving infants and toddlers with suspected airway disease without an objective clinical assessment.
To address this diagnostic gap, Swiss researchers from University Children’s Hospital Zurich (Kispi) and Empa have launched a collaborative 4-year project to develop a noninvasive, pain-free diagnostic protocol that combines breath analysis and genetic testing for infants and young children, according to the research partners.
Without reliable diagnostic tools in early childhood, clinicians face significant treatment challenges.
“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,” said Alexander Möller, senior consultant in pneumology at the University Children’s Hospital Zurich (Kispi). “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.”
Breath Analysis and Molecular Traces
The project relies on a multi-omics framework, leveraging previous research demonstrating that exhaled air contains molecular indicators of airway inflammation and that asthma has a pronounced genetic component, according to the announcement. The planned protocol involves two diagnostic components: a buccal swab for DNA testing and exhaled breath analysis using mass spectrometry.
The 4-year initiative is structured into 5 phases. In the initial two phases, Kispi is recruiting 180 children aged 2 to 4 years for a prospective longitudinal observational study, including 120 patients presenting with recurrent respiratory symptoms and 60 healthy control subjects, according to the researchers.
Participants breathe into a specialized collection bag, and the exhaled air is evaluated using a high-resolution time-of-flight mass spectrometer. Researchers at Kispi built a machine learning model to evaluate the data, identify disease-specific molecules, and generate predictive models regarding which children will develop asthma.
“Once they reach the age of five, we verify this prediction using the established diagnostic protocol,” said Alexander Möller, senior consultant in pneumology at Kispi.
Targeted Genetic Variant Panels
Later phases of the project will focus on characterizing asthma-associated genetic variants to construct a targeted gene panel, avoiding the expense and complexity of whole-genome sequencing.
“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,” said Marija Buljan, project leader and researcher with the Multi-Omics for Healthcare Materials team at Empa.
Empa investigators are designing a computational model to map cellular signaling pathways, focusing on the specific immune cells that drive airway symptoms in most pediatric asthma cases.
“The map of cellular signaling 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,” said Marija Buljan, project leader at Empa. Researchers are validating these pathway models through cell-based laboratory experiments to isolate key disease-related genes.
The final gene panel will be confirmed by collecting buccal swabs from parent-child pairs already diagnosed with asthma to verify the presence of the candidate gene variants, according to the project team.
Implications for Pediatric Pulmonary Care
If validated, the diagnostic strategy could substantially alter pediatric respiratory care by expediting treatment, avoiding emergency care, and refining medication stewardship.
“That would be a quantum leap for pediatric pulmonology,” said Alexander Möller, senior consultant in pneumology at Kispi. “With an early diagnosis, we could largely relieve affected toddlers of their asthmatic symptoms and prevent hospital admissions. At the same time, it would minimize the risk of non-asthmatic children being unnecessarily prescribed cortisone.”
The molecular findings could also aid the creation of future therapeutics. “A better understanding of the cellular mechanisms underlying asthma could serve as a basis for developing targeted and well-tolerated medications,” said Marija Buljan, project leader at Empa.
Investigators estimate that it will take another 5 to 10 years before the combined protocol is finalized, fully validated, and implemented in routine pediatric practice.
