New international research led by Edith Cowan University has identified a key difference in the biochemistry of people with and without asthma, opening new avenues to investigate more effective treatments for the condition.
Urine samples from more than 600 participants across 11 countries were collected and analysed as part of U-BIOPRED, the first large-scale, Europe-wide initiative to identify and better understand different dysregulated metabolic processes in relation to asthma severity and medication.
The results, published July 1st in the European Respiratory Journal, showed that severe asthmatics have a distinct metabolite profile detectable in their urine, compared to mild-to-moderate asthmatics and healthy individuals, with similar, significant differences also observed between non-treated asthmatic patients and those prescribed oral corticosteroids (OCS).
Further analyses revealed that carnitine, a small water-soluble molecule which plays an important role in cellular energy generation and immune responses, was lower in severe asthmatics, and demonstrated the strongest OCS-independent decrease in disease severity.
Lead author, Dr Stacey Reinke from ECU’s Centre for Integrative Metabolomics and Computational Biology, said this is an important discovery that could lead to more effective treatments for the world’s 262 million asthma sufferers.
“It is vital asthma treatment is improved… asthma affects 2.7 million Australians and there were 417 asthma-related deaths in Australia in 2020,” Dr Reinke said.
“To identify and develop new treatment options, we first need to better understand the underlying mechanisms of the disease, [and] in this case, we were able to use the urinary metabolome of asthmatics to identify fundamental differences in energy metabolism that may represent a target for new interventions in asthma control.”
Dr Reinke said that examining the body’s chemical profile, or ‘metabolome’, could provide a snapshot of a person’s current physiological state and gives useful insight into disease processes.
“It can be difficult and invasive to investigate the lungs directly but fortunately they contain a lot of blood vessels – therefore, any biochemical changes in the lungs can enter the blood stream, and then be excreted through the urine,” Dr Reinke said.
“Urine has been successfully used to investigate local physiology in the lung and is well suited to clinical applications owing to accessibility and ease of collection.”
Mass spectrometry-based metabolomics in blood and urine has identified molecular signatures associated with both adult and paediatric asthma, as well as detecting metabolic signatures associated with aspirin-exacerbated respiratory disease, disease severity, bronchodilator response, pulmonary function, exacerbation and corticosteroid resistance.
OCS treatment was of particular interest as its long-term use is associated with multiple side effects including osteoporosis, adrenal suppression, metabolic disorders, psychiatric disorders and infection.
“In the current study, OCS treatment was associated with a difference in 25% of the observed metabolites, further highlighting the importance of evaluating this confounder in molecular studies,” the research team concluded.
“Short-chain carnitines represented the strongest metabolic signature associated with asthma severity, decreased in an OCS-independent manner, and were temporally stable, providing a metabolic link to the mitochondrial dysfunction associated with severe asthma.”
Carnitine was the only metabolite cluster unaffected by OCS treatment and findings in both sputum and bronchial brushings supported the observed systemic dysregulation in carnitine metabolism.
“These are preliminary results, but we will continue to investigate carnitine metabolism to evaluate its potential as a new asthma treatment target,” Dr Reinke said.