ASTHMA is a complex respiratory condition characterised by inflammation and oxidative stress in the airways. One of the hallmarks of severe asthma is the depletion of antioxidant defences, including glutathione (GSH) and superoxide dismutase (SOD), both of which help neutralise reactive oxygen species (ROS). When these defences fail, radical-induced lipid oxidation can damage DNA, proteins, and lipids, processes now thought to contribute directly to asthma pathogenesis.
Pseudo Leukotrienes as Biomarkers of Asthma Severity
Recent research has identified a new family of biomolecules known as pseudo leukotrienes (øLTs), which appear to form through oxidative damage to arachidonate, a fatty acid present in cell membranes. These pseudo leukotrienes mimic the structure and function of cysteinyl leukotrienes (CysLTs), inflammatory molecules long associated with airway constriction and mucus production in asthma.
The study found that urinary øLT levels were significantly elevated, four- to five-fold higher, in patients with severe asthma compared to healthy controls. Similarly, allergen exposure in mice led to a 100% increase in pulmonary øLT levels. Importantly, these pseudo leukotrienes activated key inflammatory pathways (ERK and Akt) in bronchial epithelial cells, and this activity was blocked by CysLT receptor antagonists such as Montelukast and Zafirlukast.
A Paradigm Shift in Asthma Pathobiology
These findings suggest that pseudo leukotrienes may play a previously unrecognised role in driving airway inflammation. Elevated urinary øLTs could therefore serve as valuable biomarkers of asthma severity, enabling non-invasive disease monitoring and assessment of treatment efficacy.
Moreover, the discovery challenges traditional views of CysLT-mediated inflammation and may help explain the effectiveness of current therapies that target these pathways. By inhibiting øLT biosynthesis or blocking their receptor-mediated effects, new strategies could emerge for managing chronic asthma and preventing progression in susceptible individuals.
This study marks a significant step forward in understanding the biochemical underpinnings of asthma, highlighting the potential of pseudo leukotrienes as both diagnostic tools and therapeutic targets.
Reference
Liu SY et al. Radical-induced lipid oxidation produces a torrent of leukotriene-like agonists in severe asthma. J Allergy Clin Immunol. 2025;DOI:10.1016/j.jaci.2025.09.027.
