Protective effect of montelukast on lower and upper respiratory tract responses to short-term cat allergen exposure

Perry, Tamara T.; Corren, Jonathan; Philip, George; Kim, Eric; Conover-Walker, Mary Kay; Malice, Marie Pierre; Massaad, Rachid; Dass, Sairia; Reiss, Theodore F.; Wood, Robert A.

doi:10.1016/s1081-1206(10)61409-3

Cited by 38 publications

(30 citation statements)

References 37 publications

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“…Furthermore, the LAR AUC for OC000459 in sequence B was greater than placebo in sequence A, suggesting again no effect of OC000459 on the LAR in sequence B. Any possible carry-over effect was also minimised by the use of a 3-week washout period, which is longer than has been used in other allergen challenge studies [12][13][14]. Additionally, there are no pharmacokinetic reasons to explain a duration of action of OC000459 after 3 weeks, as the terminal half-life is 13 h (personal communication) and there are no pharmacologically active metabolites of this drug.…”

Section: Discussionmentioning

confidence: 97%

Inhibition of the asthmatic allergen challenge response by the CRTH2 antagonist OC000459

et al. 2012

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CRTH2 (chemoattractant receptor expressed on T-helper (Th) type 2 cells) is a Gprotein-coupled receptor expressed by Th2 lymphocytes and eosinophils that mediates prostaglandin (PG)D 2 -driven chemotaxis. We studied the efficacy of the oral CRTH2 antagonist OC000459 in steroid-naïve asthmatic patients.A randomised, double-blind, placebo-controlled, two-way crossover study of 16 days' treatment with OC000459 (200 mg twice daily) on the late (LAR) and early (EAR) asthmatic responses to bronchial allergen challenge was conducted, with 16 subjects completing the study.There was a 25.4% (95% CI 5.1-45.6%) reduction in the LAR area under the curve (AUC) for change in forced expiratory volume in 1 s with OC000459 compared with placebo (p50.018) but no effect on the EAR. Sputum eosinophil counts at 1 day post-allergen challenge were lower after OC000459 treatment (p50.002). PGD 2 -induced blood eosinophil shape change ex vivo was assessed at day 7 (n57). The AUC of eosinophil shift for OC000459 was lower than placebo; the mean difference was -33.6% (95% CI -66.8--0.4%; p50.048).OC000459 treatment inhibited LAR and post-allergen increase in sputum eosinophils. This CRTH2 antagonist appears to inhibit allergic inflammation in asthma.

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Section: Discussionmentioning

confidence: 97%

Inhibition of the asthmatic allergen challenge response by the CRTH2 antagonist OC000459

et al. 2012

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“…In these studies, montelukast was demonstrated to improve pulmonary function within 3-12 h after ingestion. This effect of a single-dose lasted up to 24 h. In other trials, the onset of action of montelukast applied orally was in the range of 1-3 days [12,15,16]. Furthermore, it was suggested that LTRA are able to reduce both the early and late asthmatic response in allergic subjects when given before allergen challenge [32].…”

Section: Discussionmentioning

confidence: 95%

“…These biological properties can be attenuated by anti-LT drugs. Reduction of inflammation and a decrease in Fe,NO following montelukast treatment is thought to occur via two distinct mechanisms involving LTs, which are: direct inhibition at the receptor level; or inhibition of eosinophil recruitment into the lung, which indirectly reduces the capacity for further release of LTs [12,13]. However, the mechanisms by which montelukast modulates nitric oxide (NO) production are not yet completely understood.…”

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confidence: 99%

Montelukast as add-on therapy to β-agonists and late airway response

Rosewich

Rose²,

Eickmeier³

et al. 2007

Eur Respir J

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The present study investigated whether single-dose oral leukotriene receptor antagonists as add-on therapy to short-acting b-agonists, immediately after allergen challenge, block the late-phase airway response.In total, 35 mild asthmatics (mean age 24 yrs, 19 males) sensitised for house dust mites underwent two courses of bronchial allergen challenge. After the early allergic response (EAR), subjects received salbutamol once and were randomly assigned to either 10 mg of montelukast or placebo (double-blind crossover). To identify a late allergic response, forced expiratory volume in one second (FEV1) was monitored over the following 8 h. Baseline exhaled nitric oxide (NO) was determined ahead of each allergen challenge.Baseline NO levels differed significantly depending on the reaction to allergen challenge. In total, 12 subjects showed no significant response, 11 only showed an EAR, and 12 had a dual response and underwent further analysis. The area under the FEV1 time-response curve 3-8 h after bronchial allergen challenge was -0.77¡1.68 from the pre-challenge values on montelukast compared with -2.47¡1.32 on placebo. The baseline exhaled NO fraction of subjects without an EAR was significantly lower than of those presenting a dual response.The results of the present study demonstrate that single-dose leukotriene receptor antagonists given orally right after the early allergic response can significantly inhibit the late allergic response after bronchial allergen challenge.

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“…30 The evidence of the value of montelukast in patients with a history of both allergic rhinitis and asthma is confined to a single randomized, crossover, placebo-controlled study in 52 patients with symptoms provoked by exposure to cats. 31 In a large study of nearly 900 patients, montelukast 10 mg was found to be inferior to fluticasone nasal spray 200 mcg per day in controlling symptoms of allergic rhinitis in patients with persistent asthma. 32 Fluticasone nasal spray became available by generic name in the first week in April 2006, 33 and the MCO cost will soon be $1.00 or less per day of therapy.…”

Section: Editorial Subjects-in This Issue and In Previous Issuesmentioning

confidence: 99%

More Evolution of the Evidence in Asthma Disease Management-SMART Versus GOAL Clinical Trials Debate the Cost-Benefit of LABA While the Value of Leukotriene Modifiers, Particularly Montelukast, Is Uncertain

Curtiss¹

2006

JMCP

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Protective effect of montelukast on lower and upper respiratory tract responses to short-term cat allergen exposure

Cited by 38 publications

References 37 publications

Inhibition of the asthmatic allergen challenge response by the CRTH2 antagonist OC000459

Inhibition of the asthmatic allergen challenge response by the CRTH2 antagonist OC000459

Montelukast as add-on therapy to β-agonists and late airway response

More Evolution of the Evidence in Asthma Disease Management-SMART Versus GOAL Clinical Trials Debate the Cost-Benefit of LABA While the Value of Leukotriene Modifiers, Particularly Montelukast, Is Uncertain

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