Image of the lungs to illustrate individuals with chronic obstructive pulmonary disease (COPD), which can be influenced by genetic variation in EPAS1 gene, which impacts oxygen saturation in the blood
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Research led by the Karolinska Institute in Stockholm has identified a urine biomarker that is lower in serious asthmatics than in individuals with a mild-to-moderate version of the inflammatory condition.

Asthma affects 262 million people around the world, but is a very variable condition with the type and severity of symptoms varying considerably between affected individuals and both genetics and environment contributing to onset. This can make it hard to tailor treatment effectively and both researchers and clinicians recognize the need to have better stratification of the different types of asthma.

Direct lung sampling is not possible in most cases and so molecular signatures that can be identified by sampling blood, urine or breath are being investigated by several groups.

“Mass spectrometry-based metabolomics in blood and urine has identified molecular signatures associated with both adult and pediatric asthma,” explain Craig Wheelock, an associate professor at the Karolinska Institute, and colleagues in the European Respiratory Journal.

“In particular, metabolomics has detected metabolic signatures associated with aspirin-exacerbated respiratory disease, disease severity, bronchodilator response, pulmonary function, exacerbation and corticosteroid resistance.”

However, while signatures linked with asthma types have been detected, few larger, longer term studies have investigated the wider validity of the detected biomarkers for use in the clinic.

In this study, Wheelock and team tested the urine of 418 patients with severe asthma, 87 with mild-to-moderate asthma and 100 healthy controls and then carried out follow-up testing 12-18 months later in 305 of the severe asthma cases. High-resolution mass spectrometry was used to collect biomarker data.

Overall, 90 metabolites were identified during the study. Of these, 40 were significantly altered in severe asthma and 23 by the use of oral corticosteroids for treatment of asthma.

The researchers found that healthy individuals and those with mild-to-moderate asthma had a very different metabolite profile compared with individuals with severe asthma. The metabolite profile linked to severe asthma also did not change significantly over time.

Of all the metabolites detected, the most significant difference in severe asthma cases was in levels of carnitine, a compound that transports fatty acids to mitochondria to produce energy and also removes byproducts of metabolism from cells. Individuals with severe asthma had significantly lower levels of carnitine, independent of oral corticosteroid use, than those with milder asthma or no asthma.

Further investigation showed that low carnitine levels were linked to mitochondrial dysfunction and reduced levels of the protein that transports carnitine around the cell, SLC22A5.

“Severe asthma occurs when someone’s asthma is uncontrolled, despite being treated with high levels of medication and/or multiple medications. To identify and develop new treatment options, we first need to better understand the underlying mechanisms of the disease,” commented Stacey Reinke, first author of the study based at Edith Cowan University in Perth, in a press statement.

“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… These are preliminary results, but we will continue to investigate carnitine metabolism to evaluate its potential as a new asthma treatment target.”

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