Biomarkers in urine can determine asthma subtypes
Researchers from Sweden’s Karolinska Institutet have used a urine test to identify and verify a patient’s type of asthma. Their study, published in the American Journal of Respiratory and Critical Care Medicine, lays the foundation for a more personalised diagnosis and may result in improved treatment of severe asthma in the future.
Asthma is characterised by chronic inflammation in the airways, which can result in symptoms including coughing, mucous formation and shortness of breath. There are many types of asthma and symptoms can vary between individuals. Treatment with steroid inhalers is often sufficient for patients with mild asthma, but for those with severe asthma it may be necessary to supplement with corticosteroid tablets.
Currently, in order to make an asthma diagnosis, a wide-ranging investigation is conducted that can consist of patient interviews, lung function tests, blood tests, allergy investigations and X-rays. As noted by Associate Professor Craig Wheelock, last author of the new study, “There are no simple methods to determine what type of asthma an individual has — knowledge that is particularly important in order to better treat patients suffering from the more severe types of the disease.”
Now Karolinska Institutet researchers have discovered a simple but clear way to make a correct diagnosis, using data from the U-BIOPRED study that included 400 participants with severe asthma, nearly 100 individuals with milder forms of asthma and 100 healthy control participants. Using a mass spectrometry-based methodology developed in the Wheelock laboratory, they were able to measure urinary metabolite levels of certain prostaglandins and leukotrienes — eicosanoid signalling molecules that are known mediators of asthmatic airway inflammation.
“We discovered particularly high levels of the metabolites of the mast cell mediator prostaglandin D2 and the eosinophil product leukotriene C4 in asthma patients with what is referred to as Type 2 inflammation,” said postdoctoral researcher Johan Kolmert, first author of the study. “Using our methodology, we were able to measure these metabolites with high accuracy and link their levels to the severity and type of asthma.
“Another discovery was that levels of these metabolites were still high in patients who were seriously ill, despite the fact that they were being treated with corticosteroid tablets. This highlights the need for alternative treatments for this group of patients.”
Measurement using a urine test provided improved accuracy relative to other measurement methods, such as certain kinds of blood tests. The researchers were also able to replicate their discovery in the urine samples of schoolchildren, with study co-leader Professor Sven-Erik Dahlén saying, “We could see that those children who had asthma with Type 2 inflammation were displaying the same profiles of metabolites in the urine as adults.”
The researchers say their study may be the largest evaluation of eicosanoid urinary metabolites conducted worldwide, and an important step towards future biomarker-guided precision medicine — particularly for those taking corticosteroid tablets, which are associated with side effects such as high blood pressure, diabetes and harm to the eyes and bones.
“To replace corticosteroid tablets, in recent times several biological medicines have been introduced to treat patients with Type 2 inflammation characterised by increased activation of mast cells and eosinophils,” Dahlén said. “However, these treatments are very expensive, so it is an important discovery that urine samples may be used to identify precisely those patients who will benefit from the Type 2 biologics.”
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