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The leukotriene-antagonist ICI-204,219 inhibits the early airway reaction to cumulative bronchial challenge with allergen in atopic asthmatics.
Eur Respir J. 1994 Feb; 7(2):324-31.ER

Abstract

The hypothesis that cysteinyl-leukotrienes (LTC4, LTD4 and LTE4) are mediators of allergen-induced airway obstruction in asthmatics was tested with the specific receptor antagonist ICI-204,219, in a double-blind, placebo-controlled, randomized, cross-over bronchoprovocation study. On three occasions, cumulative bronchial challenge with specific allergen was performed in 10 males with mild allergic asthma. The first control session established the baseline provocative dose of allergen producing a decrease in forced expiratory volume in one second (FEV1) by 20% (PD20FEV1). The two rechallenges were performed 2 h after oral administration of placebo or 20 mg of ICI-204,219. The allergen dose-response relations were highly reproducible, producing PD20 values at the control session and after placebo treatment which varied by no more than 0.7-1.3 fold (95% confidence interval (95% CI)). After ICI-204,219, the median cumulated allergen dose was 5.5 fold higher, and the group geometric mean PD20 was increased 2.5 times. Furthermore, the recovery time after the immediate bronchoconstriction was shorter (40 vs 60 min). The wheal and flare responses to intradermally injected LTD4 were somewhat inhibited by ICI-204,219, whereas responses to histamine were unaffected. However, the findings suggest that skin testing with LTD4 is unlikely to predict the degree of leukotriene-antagonism in the airways. The findings confirm and extend the indications that cysteinyl-leukotrienes are important mediators of allergen-induced airway obstruction, and that leukotriene-antagonists should be evaluated as a potential new therapy in allergic asthma.

Authors+Show Affiliations

Dept of Thoracic Medicine, Karolinska Hospital, Stockholm, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

8162986

Citation

Dahlén, B, et al. "The Leukotriene-antagonist ICI-204,219 Inhibits the Early Airway Reaction to Cumulative Bronchial Challenge With Allergen in Atopic Asthmatics." The European Respiratory Journal, vol. 7, no. 2, 1994, pp. 324-31.
Dahlén B, Zetterström O, Björck T, et al. The leukotriene-antagonist ICI-204,219 inhibits the early airway reaction to cumulative bronchial challenge with allergen in atopic asthmatics. Eur Respir J. 1994;7(2):324-31.
Dahlén, B., Zetterström, O., Björck, T., & Dahlén, S. E. (1994). The leukotriene-antagonist ICI-204,219 inhibits the early airway reaction to cumulative bronchial challenge with allergen in atopic asthmatics. The European Respiratory Journal, 7(2), 324-31.
Dahlén B, et al. The Leukotriene-antagonist ICI-204,219 Inhibits the Early Airway Reaction to Cumulative Bronchial Challenge With Allergen in Atopic Asthmatics. Eur Respir J. 1994;7(2):324-31. PubMed PMID: 8162986.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The leukotriene-antagonist ICI-204,219 inhibits the early airway reaction to cumulative bronchial challenge with allergen in atopic asthmatics. AU - Dahlén,B, AU - Zetterström,O, AU - Björck,T, AU - Dahlén,S E, PY - 1994/2/1/pubmed PY - 1994/2/1/medline PY - 1994/2/1/entrez SP - 324 EP - 31 JF - The European respiratory journal JO - Eur Respir J VL - 7 IS - 2 N2 - The hypothesis that cysteinyl-leukotrienes (LTC4, LTD4 and LTE4) are mediators of allergen-induced airway obstruction in asthmatics was tested with the specific receptor antagonist ICI-204,219, in a double-blind, placebo-controlled, randomized, cross-over bronchoprovocation study. On three occasions, cumulative bronchial challenge with specific allergen was performed in 10 males with mild allergic asthma. The first control session established the baseline provocative dose of allergen producing a decrease in forced expiratory volume in one second (FEV1) by 20% (PD20FEV1). The two rechallenges were performed 2 h after oral administration of placebo or 20 mg of ICI-204,219. The allergen dose-response relations were highly reproducible, producing PD20 values at the control session and after placebo treatment which varied by no more than 0.7-1.3 fold (95% confidence interval (95% CI)). After ICI-204,219, the median cumulated allergen dose was 5.5 fold higher, and the group geometric mean PD20 was increased 2.5 times. Furthermore, the recovery time after the immediate bronchoconstriction was shorter (40 vs 60 min). The wheal and flare responses to intradermally injected LTD4 were somewhat inhibited by ICI-204,219, whereas responses to histamine were unaffected. However, the findings suggest that skin testing with LTD4 is unlikely to predict the degree of leukotriene-antagonism in the airways. The findings confirm and extend the indications that cysteinyl-leukotrienes are important mediators of allergen-induced airway obstruction, and that leukotriene-antagonists should be evaluated as a potential new therapy in allergic asthma. SN - 0903-1936 UR - https://www.unboundmedicine.com/medline/citation/8162986/The_leukotriene_antagonist_ICI_204219_inhibits_the_early_airway_reaction_to_cumulative_bronchial_challenge_with_allergen_in_atopic_asthmatics_ L2 - http://erj.ersjournals.com/cgi/pmidlookup?view=long&pmid=8162986 DB - PRIME DP - Unbound Medicine ER -