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Inhibition of exercise-induced bronchoconstriction by MK-571, a potent leukotriene D4-receptor antagonist.
N Engl J Med. 1990 Dec 20; 323(25):1736-9.NEJM

Abstract

BACKGROUND

Exercise is a common stimulus of bronchoconstriction in subjects with asthma, who also have bronchoconstriction after inhaling the sulfidopeptide leukotriene D4 (LTD4). The purpose of this study was to investigate the importance of LTD4 as a mediator of exercise-induced bronchoconstriction.

METHODS

In a double-blind, randomized, crossover study, 12 subjects with stable asthma were treated intravenously with MK-571 (160 mg), a selective and potent LTD4-receptor antagonist, or placebo, 20 minutes before each of two challenges involving exercise at a level previously demonstrated to cause a fall of at least 20 percent in the forced expiratory volume in one second (FEV1). The two exercise challenges were separated by one week. The results of the challenges were expressed as both the maximal fall in FEV1 after exercise and the time to recovery from bronchoconstriction.

RESULTS

Treatment with MK-571 attenuated exercise-induced bronchoconstriction in all the subjects. The mean (+/- SEM) maximal percent decrease in FEV1 after exercise was 25.2 +/- 3.5 percent in the subjects taking placebo and 9.2 +/- 2.5 percent in the subjects taking MK-571 (P less than 0.001). The mean percent inhibition for the entire group was 69.5 percent. The mean time to recovery after exercise was 33.4 +/- 4.0 minutes in the placebo group and 8.4 +/- 2.5 minutes in the MK-571 group (P less than 0.001).

CONCLUSIONS

This study demonstrates that pretreatment with a potent and selective LTD4 antagonist markedly attenuates exercise-induced bronchoconstriction, and it suggests that LTD4 is a major mediator of this type of bronchoconstriction.

Authors+Show Affiliations

Department of Medicine, McMaster University, Hamilton, Ont., Canada.No affiliation info availableNo affiliation info availableNo 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

2174121

Citation

Manning, P J., et al. "Inhibition of Exercise-induced Bronchoconstriction By MK-571, a Potent Leukotriene D4-receptor Antagonist." The New England Journal of Medicine, vol. 323, no. 25, 1990, pp. 1736-9.
Manning PJ, Watson RM, Margolskee DJ, et al. Inhibition of exercise-induced bronchoconstriction by MK-571, a potent leukotriene D4-receptor antagonist. N Engl J Med. 1990;323(25):1736-9.
Manning, P. J., Watson, R. M., Margolskee, D. J., Williams, V. C., Schwartz, J. I., & O'Byrne, P. M. (1990). Inhibition of exercise-induced bronchoconstriction by MK-571, a potent leukotriene D4-receptor antagonist. The New England Journal of Medicine, 323(25), 1736-9.
Manning PJ, et al. Inhibition of Exercise-induced Bronchoconstriction By MK-571, a Potent Leukotriene D4-receptor Antagonist. N Engl J Med. 1990 Dec 20;323(25):1736-9. PubMed PMID: 2174121.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of exercise-induced bronchoconstriction by MK-571, a potent leukotriene D4-receptor antagonist. AU - Manning,P J, AU - Watson,R M, AU - Margolskee,D J, AU - Williams,V C, AU - Schwartz,J I, AU - O'Byrne,P M, PY - 1990/12/20/pubmed PY - 1990/12/20/medline PY - 1990/12/20/entrez SP - 1736 EP - 9 JF - The New England journal of medicine JO - N Engl J Med VL - 323 IS - 25 N2 - BACKGROUND: Exercise is a common stimulus of bronchoconstriction in subjects with asthma, who also have bronchoconstriction after inhaling the sulfidopeptide leukotriene D4 (LTD4). The purpose of this study was to investigate the importance of LTD4 as a mediator of exercise-induced bronchoconstriction. METHODS: In a double-blind, randomized, crossover study, 12 subjects with stable asthma were treated intravenously with MK-571 (160 mg), a selective and potent LTD4-receptor antagonist, or placebo, 20 minutes before each of two challenges involving exercise at a level previously demonstrated to cause a fall of at least 20 percent in the forced expiratory volume in one second (FEV1). The two exercise challenges were separated by one week. The results of the challenges were expressed as both the maximal fall in FEV1 after exercise and the time to recovery from bronchoconstriction. RESULTS: Treatment with MK-571 attenuated exercise-induced bronchoconstriction in all the subjects. The mean (+/- SEM) maximal percent decrease in FEV1 after exercise was 25.2 +/- 3.5 percent in the subjects taking placebo and 9.2 +/- 2.5 percent in the subjects taking MK-571 (P less than 0.001). The mean percent inhibition for the entire group was 69.5 percent. The mean time to recovery after exercise was 33.4 +/- 4.0 minutes in the placebo group and 8.4 +/- 2.5 minutes in the MK-571 group (P less than 0.001). CONCLUSIONS: This study demonstrates that pretreatment with a potent and selective LTD4 antagonist markedly attenuates exercise-induced bronchoconstriction, and it suggests that LTD4 is a major mediator of this type of bronchoconstriction. SN - 0028-4793 UR - https://www.unboundmedicine.com/medline/citation/2174121/Inhibition_of_exercise_induced_bronchoconstriction_by_MK_571_a_potent_leukotriene_D4_receptor_antagonist_ L2 - https://www.nejm.org/doi/10.1056/NEJM199012203232504?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -