Effects of histamine and leukotriene antagonism on mannitol and adenosine monophosphate challenges

Currie, G. P., Haggart, K., Lee, D. K. C., Fowler, S. J., Wilson, A. M., Brannan, J. D., Anderson, S. D. and Lipworth, B. J. (2003) Effects of histamine and leukotriene antagonism on mannitol and adenosine monophosphate challenges. Clinical and Experimental Allergy, 33 (6). pp. 783-788. ISSN 1365-2222

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Abstract

Background: Airway hyper-responsiveness (AHR) to indirect stimuli is a useful non-invasive surrogate inflammatory marker in the evaluation of asthma, while histamine and cysteinyl leukotrienes are important inflammatory mediators. Objective: To evaluate AHR to indirect bronchoconstrictor stimuli and time taken to recover following single doses of montelukast 10mg and desloratadine 5mg in combination, montelukast 10mg alone and placebo. Methods: Fifteen mild-to-moderate persistent asthmatics completed a randomized, double-blind, cross-over study. Patients received encapsulated montelukast 10mg/desloratadine 5mg combination, montelukast 10mg alone and placebo, 10–14h prior to challenge on two separate occasions. The mannitol threshold dose, AMP threshold concentration and recovery times after challenge were measured along with lung function. Results: Compared to placebo, montelukast/desloratadine conferred improvements (P < 0.05) in adenosine monophosphate (AMP) threshold concentration and mannitol threshold dose: a 3.2-fold (95% CI 2.2–4.6) and 2.4-fold (95% CI 1.7–3.3) difference, respectively, while compared to montelukast this amounted to a 2.0-fold (95% CI 1.2–3.4) and 1.5-fold (95% CI 1.1–2.4) improvement, respectively. Montelukast was not significantly different from placebo. Both montelukast/desloratadine and montelukast compared to placebo, shortened recovery following both challenges (P < 0.05): a 27-min (95% CI 17–37) and 29-min (95% CI 20–36) reduction, respectively, for AMP, and a 27-min (95% CI 17–37) and 26-min (95% CI 17–35) reduction, respectively for mannitol. Conclusion: The dissociated effects of single doses of montelukast alone but not montelukast/desloratadine combination on AHR and recovery time, highlights the relative roles of histamine in initiating the bronchoconstrictor response and cysteinyl leukotrienes in sustaining it. Similar improvements in AHR and recovery time were observed following both indirect bronchoconstrictor stimuli.

Item Type:	Article
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Respiratory and Airways Group Faculty of Medicine and Health Sciences > Research Groups > Cardiovascular and Metabolic Health Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health Faculty of Medicine and Health Sciences > Research Groups > Norwich Clinical Trials Unit Faculty of Medicine and Health Sciences > Research Centres > Population Health
Depositing User:	EPrints Services
Date Deposited:	25 Nov 2010 11:09
Last Modified:	28 Mar 2025 04:33
URI:	https://ueaeprints.uea.ac.uk/id/eprint/12472
DOI:	10.1046/j.1365-2222.2003.01688.x

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