For decades, leukotrienes - molecules derived from white blood cells - were blamed as one of the main causes of asthma symptoms like airway constriction and wheezing. Drugs like montelukast (Singulair) target their receptors based on this view.
New research from Case Western Reserve University (led by chemist Robert Salomon, PhD) challenges that. Published in the Journal of Allergy and Clinical Immunology (2025), the team identified pseudo leukotrienes (øLTs)—structurally similar but formed differently via uncontrolled free radical oxidation of lipids.
“The free radical process is almost like an explosion or a fire,” said Salomon, who is also professor of ophthalmology in the Case Western Reserve School of Medicine. “It’s just like when oxygen reacts with fuel and you get flames. It can easily get out of control.” The leukotrienes and their mimics initiate inflammation by fitting into a receptor, like a key in an ignition, starting a molecular cascade that constricts the airways of asthmatics.
Key findings:
Pseudo leukotrienes øLTs were detected in urine of asthma patients.
Levels were 4–5 times higher in severe asthma vs. controls, correlating with disease severity. Not only were pseudo leukotrienes øLTs found in the asthma patients’ urine, but also the amounts correlated directly to the severity of the disease.
They activate inflammatory pathways (e.g., ERK/Akt) in airway cells, blocked by existing leukotriene receptor antagonists.
This suggests pseudo leukotrienes øLTs may drive some of the airway inflammation. Targeting the free radical process could lead to safer, more precise treatments, avoiding broad suppression of inflammation.
Pseudo leukotrienes øLTs may have a potential as a urine biomarker for severity and monitoring. The discovery may extend to other oxidative stress-related conditions (e.g., COPD, neurological diseases).
Asthma Treatment Options (click to enlarge the image).
References:
https://www.sciencedirect.com/science/article/pii/S0091674925010267