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Lipid Biomarkers in Urine Can Determine Asthma Type
January 13, 2021

Monitoring of urinary eicosanoids can assist with the molecular phenotyping of adult and adolescent asthma, according to a study published in the American Journal of Respiratory and Critical Care Medicine.

Currently, in order to make an asthma diagnosis, a wide-ranging investigation is conducted that can consist of multiple elements including patient interviews, lung function tests, blood tests, allergy investigations, and x-rays.

“There are no simple methods to determine what type of asthma an individual has,” said Craig Wheelock, PhD, Karolinska Institutet, Stockholm, Sweden. “[This] knowledge is particularly important in order to better treat patients suffering from the more severe types of the disease.”

For the current study, Johan Kolmert, PhD, Karolinska Institutet, and colleagues used a mass spectrometry-based methodology to measure urinary metabolite levels of prostaglandins, cysteinyl leukotrienes, and isoprostanes in participants from the Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes (U-BIOPRED) study. The cohort included 86 adults with mild-to-moderate asthma, 411 with severe asthma, and 100 healthy controls.

Validation was performed internally in 302 patients with severe asthma who were followed up with after 12 to 18 months, and externally in 95 adolescents with asthma.

“We discovered particularly high levels of the metabolites of the mast cell mediator prostaglandin D2 and the eosinophil product leukotriene C4 in patients [with asthma who had] type 2 inflammation,” said Dr. Kolmert. “Using our methodology, we were able to measure these metabolites with high accuracy and link their levels to the severity and type of asthma.”

In addition to the increased eicosanoid metabolite levels associated with asthma type and severity, the study found that measurement using a urine test provides improved accuracy relative to other measurement methods, for example certain kinds of blood tests.

“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[s],” explained Dr. Kolmert. “This highlights the need for alternative treatments for this group of patients.”

In the validation cohort of adolescents, the researchers found that those who had asthma with type 2 inflammation displayed the same profiles of metabolites in their urine as adults.

According to the researchers, this study of severe asthma could be an important step towards future biomarker-guided precision medicine. While treatment with steroid inhalers is often sufficient for patients with mild asthma, corticosteroids, which are associated with various side effects, are often necessary for those with severe asthma.
“To replace corticosteroid[s], several biological medicines have been introduced to treat patients with type 2 inflammation characterised by increased activation of mast cells and eosinophils,” concluded Sven-Erik Dahlén, MD, Karolinska Institutet. “However, these treatments are very expensive, so it is an important discovery that urine samples may be used to identify [which] patients will benefit from type 2 biologics.”

Reference: http://dx.doi.org/10.1164/rccm.201909-1869OC

SOURCE: Karolinska Institutet