The role of leukotrienes in asthma and allergic rhinitis

Abstract

The recent elucidation of the inflammatory responses underlying asthma and allergic rhinitis has stimulated the development of new anti-asthma treatments, including numerous antileukotriene agents. These agents, which represent a new direction in targeted therapy, either antagonize the leukotriene receptor (e.g. zafirlukast) or block the synthesis of leukotrienes (e.g. zileuton). They have been used in preclinical and clinical studies involving normal subjects and patients with asthma or allergic rhinitis. These studies have generally supported the putative role of leukotrienes in the mechanisms of asthma and allergic rhinitis. With respect to asthma, the leukotrienes also appear to function as potent mediators of bronchoconstriction. The above cited results indicate that antileukotriene agents offer incremental improvements in airway caliber and may also attenuate the inflammatory response. Because they are orally administered, they should have the additional benefit of increasing patient compliance relative to other currently available treatments. In their current form, however, they may not be expected to replace the mainstays of current therapy but to act rather, as adjuvant therapy. Patients with relatively mild asthma may be able to achieve efficacy with an antileukotriene agent plus as needed beta-adrenergic agonists; patients with more significant disease might use antileukotriene agents as a supplement to another anti-inflammatory agent, such as cromolyn, nedocromil, or corticosteroids. Studies of asthma patients have confirmed the ability of antileukotriene agents to attenuate asthma-associated bronchoconstriction. Antileukotriene agents appear to significantly attenuate aspirin-, allergen-, and exercise-induced asthma, as well as the signs and symptoms of nocturnal and chronic asthma; they may have efficacy in other inflammation-associated disorders such as allergic rhinitis as well.

A Population Pharmacokinetic Model for Montelukast Disposition in Adults and Children

“…Cysteinyl-leukotrienes, lipid mediators released from inflammatory cells, produce airway edema, mucus secretion, and eosinophil migration; reactions associated with the major findings of airway inflammation in asthma (2)(3)(4). Cysteinylleukotrienes levels are thought to be elevated in patients with acute asthma, providing a rationale for treatment with antileukotriene agents during acute exacerbations.…”

Different Roles of Histamine and Leukotriene C4in the Airways Between Patients with Atopic and Nonatopic Asthma

“…The HPLC analysis for extraction and quantification of LTC, was performed by a method by Lam et al (8,13,14) The extraction of LTC, was performed using a C18 Sep-Pak (Waters Associates, Milford, MA). The concentration of LTC, was analyzed by an HPLC system, model 510 (Waters Associates), equipped with an ultraviolet detector.…”

Effects of asthma treatment: the present and future

“…Since the upper and lower airways have a direct anatomical connection, share similar epithelial lining and release similar inflammatory mediators [64,65], it has been suggested that asthma and allergic rhinitis -which co-exist in up to 40% of individuals -represent a continuation of the same inflammatory disease process. Moreover, successful treatment of allergic rhinitis can confer benefits in overall asthma control [66,67].…”