Leukotriene Modulating Therapies in Asthma and Allergic Conditions

Leukotriene modulating therapies target a key inflammatory axis in asthma and related allergic disorders. Leukotrienes are lipid mediators generated from arachidonic acid via the 5-lipoxygenase pathway and include cysteinyl leukotrienes that drive bronchoconstriction, vascular permeability, mucus hypersecretion and eosinophil recruitment. Two principal approaches exist: leukotriene receptor antagonists, such as montelukast, zafirlukast and pranlukast, which block CysLT1 receptors; and 5-lipoxygenase inhibitors, typified by zileuton, which prevent leukotriene synthesis. Receptor antagonists are widely used as oral add-on agents in mild-to-moderate asthma, exercise-induced bronchoconstriction, aspirin-exacerbated respiratory disease and allergic rhinitis, offering steroid-sparing benefits and ease of administration. However, interindividual variability in response and emerging concerns over neuropsychiatric events have prompted efforts to stratify patients by inflammatory phenotype. Current research is exploring novel dual-inhibition strategies, next-generation receptor antagonists with improved safety profiles and integration of leukotriene blockade into biologic-refractory asthma management.

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Leukotriene Modulating Therapies in Asthma and Allergic Conditions publication trend

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Technical terms

Leukotriene: A pro-inflammatory lipid mediator derived from arachidonic acid by 5-lipoxygenase, implicated in bronchoconstriction and vascular permeability.

Cysteinyl leukotriene receptor (CysLT1): A G-protein-coupled receptor on airway smooth muscle and inflammatory cells that binds leukotrienes C4, D4 and E4 to induce bronchospasm and inflammation.

Leukotriene receptor antagonist (LTRA): An oral agent that competitively inhibits CysLT1 receptors, reducing leukotriene-mediated effects in asthma and allergic rhinitis.

5-Lipoxygenase (5-LOX): The enzyme that catalyses the conversion of arachidonic acid to leukotriene A4, the precursor of cysteinyl leukotrienes and leukotriene B4.

Aspirin-exacerbated respiratory disease (AERD): A clinical phenotype of asthma characterised by sensitivity to aspirin and other non-steroidal anti-inflammatory drugs, often responsive to leukotriene inhibition.

References

1. Analysis of Neuropsychiatric Diagnoses After Montelukast Initiation. JAMA Network Open (2022).
2. Adverse drug reactions of leukotriene receptor antagonists in children with asthma: a systematic review. BMJ Paediatrics Open (2021).
3. Role of Montelukast in Asthma and Allergic rhinitis patients. Pakistan Journal of Medical Sciences (2020).