Effects of single-dose zileuton on bronchial hyperresponsiveness in asthmatic patients treated with inhaled corticosteroids

Dekhuijzen, P.N.R.; Bootsma, Gerben; Wielders, Pascal; Berg, Lynn; Festen, J.; Herwaarden, C.L.A. van

doi:10.1183/09031936.97.10122749

Cited by 18 publications

(10 citation statements)

References 27 publications

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“…Bronchial hyperresponsiveness to methacholine was significantly reduced with the use of Cys-LT antagonists in certain studies, 50,51 even in patients on concurrent treatment with inhaled corticosteroids. 52 In contrast, montelukast exerted no significant effect on methacholine reactivity in a 12-week treatment of 110 adult asthmatic patients. 53 EIB was significantly attenuated by Cys-LT modifiers.…”

Section: Effects Of Cys-lts Blockade In Models Of Asthmamentioning

confidence: 91%

Leukotriene Modifiers in Pediatric Asthma Management

Bisgaard

2001

Pediatrics

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Cysteinyl leukotrienes (Cys-LTs) are mediators released in asthma and virus-induced wheezing. Corticosteroids appear to have little or no effect on this release in vivo. Cys-LTs are both direct bronchoconstrictors and proinflammatory substances that mediate several steps in the pathophysiology of chronic asthma, including inflammatory cell recruitment, vascular leakage, and possibly airway remodeling. Blocking studies show that Cys-LTs are pivotal mediators in the pathophysiology of asthma. Cys-LTs are key components in the early and late allergic airway response and also contribute to bronchial obstruction after exercise and hyperventilation of cold, dry air in asthmatics. LT modifiers reduce airway eosinophil numbers and exhaled nitric oxide levels. Together these findings support an important role for the Cys-LTs in the asthma airway inflammation. Cys-LT receptor antagonists (Cys-LTRA) are generally well-tolerated. Phase III randomized, controlled clinical trials (RCT) show that LT modifiers are moderately effective, apparently with a particular between-patient variability in their clinical response. The clinical effects of LT modifiers are additive to those of beta-agonists and corticosteroids. The onset of action of LT modifiers is within 1 to several days, and not rapid enough to make them useful as rescue treatment. Although LT modifiers possess some antiinflammatory activity, they cannot substitute for corticosteroids for inflammation control. LT modifiers are alternatives to long-acting beta-agonists as complementary treatment to inhaled corticosteroids in pediatric asthma management because they provide bronchodilation and bronchoprotection without development of tolerance, and complement the antiinflammatory activity unchecked by steroids. In addition, the Cys-LTRA montelukast has been shown to ameliorate asthmatic symptoms and provide bronchoprotection in asthmatic preschool children from 2 years of age, which is of particular importance in this difficult-to-manage group of asthmatics. Given their efficacy, antiinflammatory activity, oral administration, and safety, LT modifiers will play an important role in the treatment of asthmatic children.

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Section: Effects Of Cys-lts Blockade In Models Of Asthmamentioning

confidence: 91%

Leukotriene Modifiers in Pediatric Asthma Management

Bisgaard

2001

Pediatrics

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“…In the histamine challenge study [114] that included patients on ICS, no improvement in baseline lung function before challenge tests was found after zileuton administration. This could be due to the high mean FEV 1 of the group that was 111% of predicted.…”

Section: Bronchodilator Effect Of Zileutonmentioning

confidence: 85%

“…Challenges were repeated twice in random order separated by at least 5 days. Neither zileuton nor placebo changed baseline airway calibre prior to bronchoprovocation, but the active drug rendered significant protection both to histamine (PC20 increased from 0.99 to 5.64 mg/ml) and to distilled water (PD20 increased from 3.10 to 9.31 ml) [114].…”

Section: Challenge Testsmentioning

confidence: 99%

Antileukotrienes in asthma: present situation

García‐Marcos

Schuster²

2001

Expert Opinion on Pharmacotherapy

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Leukotrienes are key mediators in asthma. Over the last 5 years, several antileukotrienes, including three receptor antagonists (montelukast, pranlukast and zafirlukast) and one 5-lipoxygenase inhibitor (zileuton), have been marketed and, to date, this class of drugs is being used widely. Still, their definite place in the asthma treatment algorithm is not yet established. These novel drugs have not yet all been evaluated in the same depth, but they have all been shown to possess anti-inflammatory properties and to be effective in chronic asthma treatment. Zafirlukast and montelukast are particularly efficacious in exercise-induced asthma and zileuton appears valuable for treating aspirin-intolerant asthmatics. Clinical comparisons to other anti-asthma drugs are still sparse. The corticosteroid-sparing effect of antileukotrienes is fairly well established except for zileuton, even though this drug has been evaluated most thoroughly in terms of its anti-inflammatory effects. Montelukast is the antileukotriene most extensively evaluated in children and zafirlukast has recently been approved for use in children in the USA, although not yet in Europe. Therapeutic regimes are quite variable depending on the drug, but all of the antileukotrienes marketed to date are taken orally; hence, compliance is usually greater than that with inhaled medication. Response to antileukotrienes appears to depend on the individual patients' characteristics, in particular on genetic polymorphisms related to leukotriene metabolism. All drugs of this class are well tolerated and only in the case of zileuton is there potential for hepatic adverse effects. The diagnosis of Churg-Strauss syndrome made among patients taking antileukotrienes seems to be more related to the withdrawal of corticosteroids than to the antileukotrienes themselves.

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“…Few other studies have been reported which make the results of the study by DEKHUIJZEN et al [6] of particular interest. As would be anticipated from studies of the effect of antileukotriene drugs on exercise [31] and cold air [32] a marked effect on the indirect challenge of nebulized distilled water was observed.…”

Section: Nc Barnesmentioning

confidence: 87%

“…Due to this effect, the results of studies assessing BHR in relation to any new drug which affects the inflammatory cascade in asthma, are always keenly awaited. Reported in this issue of the European Respiratory Journal, is a study on the effects of the 5-lipoxygenase inhibitor zileuton on BHR [6]. How does this study relate to our current understanding of the role, if any, of leukotrienes, in the pathogenesis of airways inflammation and BHR?…”

Section: Nc Barnesmentioning

confidence: 99%

Are leukotrienes involved in causing bronchial hyperresponsiveness?

Nc¹

1997

Eur Respir J

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Effects of single-dose zileuton on bronchial hyperresponsiveness in asthmatic patients treated with inhaled corticosteroids

Cited by 18 publications

References 27 publications

Leukotriene Modifiers in Pediatric Asthma Management

Leukotriene Modifiers in Pediatric Asthma Management

Antileukotrienes in asthma: present situation

Are leukotrienes involved in causing bronchial hyperresponsiveness?

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