Monitoring urinary eicosanoids a noninvasive approach for molecular phenotyping of asthma

Monitoring urinary eicosanoids provides a noninvasive approach to identify type 2 asthma and for molecular phenotyping of asthma in adolescents and adults, according to results published in the American Journal of Respiratory and Critical Care Medicine.

“There are currently 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,” Craig E. Wheelock, PhD, associate professor in the department of medical biochemistry and biophysics at Karolinska Institutet in Stockholm, told Healio. “There is accordingly an acute need for diagnostics for subphenotyping of asthma. For example, biologic medicines are increasingly being used to treat asthma and can replace corticosteroids, which have a number of side effects. However, these treatments are expensive, so it is important to precisely identify those patients who will benefit from biologics.”

Researchers conducted the U-BIOPRED study to quantify urinary metabolites of prostaglandins, cysteinyl leukotrienes and isoprostanes. The study enrolled 86 adults with mild to moderate asthma (median age, 43 years; 50% women), 302 adults with severe nonsmoking asthma (median age, 53 years; 66% women), 109 adult smokers and ex-smokers with severe asthma (median age, 55 years; 51% women), and 100 healthy controls (median age, 35 years; 39% women). The researchers performed internal validation in 302 participants with severe asthma with follow-up at 12 to 18 months and external validation in 95 adolescents with asthma.

In participants with mild to moderate asthma, eicosanoid concentrations were greater compared with healthy controls (P < .0001). There were further elevations in eicosanoid concentrations in participants with severe asthma.

In male nonsmokers with asthma, prostaglandin eicosanoid metabolite concentrations were the same or lower compared with healthy controls.

Metabolite concentrations were unchanged in those with asthma who adhered to oral corticosteroid treatments. Participants with severe asthma treated with omalizumab (Xolair, Genentech) had lower cysteinyl leukotrienes and prostaglandin eicosanoid concentrations.

Lower lung function and increased amounts of exhaled nitric oxide and eosinophil markers in blood, sputum and urine were associated with high cysteinyl leukotrienes and prostaglandin eicosanoid concentrations in adolescents and adults with asthma, according to the researchers.

At the follow-up visit, type 2 asthma associations were reproduced and observed to be as sensitive as established biomarkers for the detection of type 2 inflammation, according to the researchers.

“Levels of urinary eicosanoid metabolites possess sufficient molecular resolution to identify a type 2 inflammation subtype of asthma,” Wheelock told Healio.

The results of this initial study are promising, but need replication in additional cohorts of different populations, Wheelock said. In addition, the researchers identified a type 2 inflammation asthma subtype, but Wheelock noted that there are other subtypes of asthma.

“There is a need to identify molecular signatures of nontype 2 inflammation, which can potentially be accomplished by increasing the molecular diversity of the phenotyping panel,” Wheelock said.

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Craig E. Wheelock, PhD, can be reached at craig.wheelock@ki.se.