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The effect of the leukotriene receptor antagonist zafirlukast on neurokinin A-induced bronchoconstriction in patients with asthma--A comparison with leukotriene D4 induced broncoconstriction.
Pulm Pharmacol Ther. 2008; 21(2):276-84.PP

Abstract

The bronchoconstriction caused by inhaled neurokinin A (NKA) in patients with asthma is indirect. The mediators involved in NKA-induced bronchoconstriction are unknown. Studies with various H1 receptor antagonists were negative, making an important contribution of histamine unlikely. To study the role of cysteinyl leukotrienes in neurokinin A-induced bronchoconstriction, we performed a randomised, double-blind, cross-over, placebo controlled trial in 12 patients with mild to moderate asthma. Zafirlukast and matching placebo were given orally, 40 mg the evening before and 40 mg the morning of assessment. In one period NKA was administered, in the other period leukotriene D4 (LTD4). Increasing concentrations of NKA and LTD4 were inhaled from a 30 L bag, after nebulization via a Mallinckrodt nebuliser. The difference between log10PC20LTD4 after treatment with placebo or zafirlukast was highly significant (p<0.0001). A trend was observed towards a difference between log10PC20 neurokinin A after treatment with placebo or zafirlukast (p=0.0741). The dose ratio for the neurokinin A provocation was 4.4 and for the LTD4 provocation 67.7. In conclusion, zafirlukast had a large inhibitory effect on LTD4-induced bronchoconstriction, but offered only limited protective effect against neurokinin A-induced bronchoconstriction. We suggest that leukotrienes play a limited role in the bronchoconstrictor effect of neurokinin A in patients with asthma.

Authors+Show Affiliations

Department of Respiratory Diseases, Ghent University Hospital, De Pintelaan 185, B 9000 Ghent, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17611132

Citation

Schelfhout, V, et al. "The Effect of the Leukotriene Receptor Antagonist Zafirlukast On Neurokinin A-induced Bronchoconstriction in Patients With asthma--A Comparison With Leukotriene D4 Induced Broncoconstriction." Pulmonary Pharmacology & Therapeutics, vol. 21, no. 2, 2008, pp. 276-84.
Schelfhout V, Van De Velde V, Pauwels R, et al. The effect of the leukotriene receptor antagonist zafirlukast on neurokinin A-induced bronchoconstriction in patients with asthma--A comparison with leukotriene D4 induced broncoconstriction. Pulm Pharmacol Ther. 2008;21(2):276-84.
Schelfhout, V., Van De Velde, V., Pauwels, R., & Joos, G. (2008). The effect of the leukotriene receptor antagonist zafirlukast on neurokinin A-induced bronchoconstriction in patients with asthma--A comparison with leukotriene D4 induced broncoconstriction. Pulmonary Pharmacology & Therapeutics, 21(2), 276-84.
Schelfhout V, et al. The Effect of the Leukotriene Receptor Antagonist Zafirlukast On Neurokinin A-induced Bronchoconstriction in Patients With asthma--A Comparison With Leukotriene D4 Induced Broncoconstriction. Pulm Pharmacol Ther. 2008;21(2):276-84. PubMed PMID: 17611132.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of the leukotriene receptor antagonist zafirlukast on neurokinin A-induced bronchoconstriction in patients with asthma--A comparison with leukotriene D4 induced broncoconstriction. AU - Schelfhout,V, AU - Van De Velde,V, AU - Pauwels,R, AU - Joos,G, Y1 - 2007/05/24/ PY - 2006/08/04/received PY - 2007/05/01/revised PY - 2007/05/06/accepted PY - 2007/7/6/pubmed PY - 2008/8/2/medline PY - 2007/7/6/entrez SP - 276 EP - 84 JF - Pulmonary pharmacology & therapeutics JO - Pulm Pharmacol Ther VL - 21 IS - 2 N2 - The bronchoconstriction caused by inhaled neurokinin A (NKA) in patients with asthma is indirect. The mediators involved in NKA-induced bronchoconstriction are unknown. Studies with various H1 receptor antagonists were negative, making an important contribution of histamine unlikely. To study the role of cysteinyl leukotrienes in neurokinin A-induced bronchoconstriction, we performed a randomised, double-blind, cross-over, placebo controlled trial in 12 patients with mild to moderate asthma. Zafirlukast and matching placebo were given orally, 40 mg the evening before and 40 mg the morning of assessment. In one period NKA was administered, in the other period leukotriene D4 (LTD4). Increasing concentrations of NKA and LTD4 were inhaled from a 30 L bag, after nebulization via a Mallinckrodt nebuliser. The difference between log10PC20LTD4 after treatment with placebo or zafirlukast was highly significant (p<0.0001). A trend was observed towards a difference between log10PC20 neurokinin A after treatment with placebo or zafirlukast (p=0.0741). The dose ratio for the neurokinin A provocation was 4.4 and for the LTD4 provocation 67.7. In conclusion, zafirlukast had a large inhibitory effect on LTD4-induced bronchoconstriction, but offered only limited protective effect against neurokinin A-induced bronchoconstriction. We suggest that leukotrienes play a limited role in the bronchoconstrictor effect of neurokinin A in patients with asthma. SN - 1094-5539 UR - https://www.unboundmedicine.com/medline/citation/17611132/The_effect_of_the_leukotriene_receptor_antagonist_zafirlukast_on_neurokinin_A_induced_bronchoconstriction_in_patients_with_asthma__A_comparison_with_leukotriene_D4_induced_broncoconstriction_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1094-5539(07)00046-6 DB - PRIME DP - Unbound Medicine ER -