Document Detail

Exercise-induced refractoriness in asthmatic subjects involves leukotriene and prostaglandin interdependent mechanisms.
MedLine Citation:
PMID:  8214949     Owner:  NLM     Status:  MEDLINE    
Exercise-induced bronchoconstriction is caused, in part, by leukotriene (LT)D4 release in asthmatic airways. Asthmatics become refractory to exercise bronchoconstriction with repeated challenges, due to inhibitory prostaglandin release. The purpose of this study was to test the hypothesis that exercise refractoriness is caused by LTD4-induced inhibitory prostaglandin release. Fourteen stable asthmatic subjects with exercise-induced bronchoconstriction were studied. On the first 2 days, subjects underwent two challenges, 1 h apart, with either exercise or inhaled LTD4. Eight subjects then took part in three double-blind, randomized, placebo-controlled, crossover studies with flurbiprofen, a prostaglandin synthetase inhibitor, to determine whether cross refractoriness occurs between exercise and LTD4, whether flurbiprofen attenuates this effect, and whether flurbiprofen attenuates LTD4 tachyphylaxis. There was a reduction in the intensity of bronchoconstriction to the second challenge both with exercise (refractoriness) and with LTD4 (tachyphylaxis). The degrees of refractoriness and tachyphylaxis were correlated (r = 0.72, p = 0.005). Flurbiprofen attenuated LTD4 tachyphylaxis. Cross refractoriness occurred between exercise and LTD4, and flurbiprofen treatment also attenuated this effect. One hour after LTD4 challenge, the mean fall in FEV1 after exercise was 12.3% (%SEM 2.3) on placebo and 17.1% (%SEM 3.8) on flurbiprofen (p = 0.027). Similarly, 1 h after exercise, the LTD4 PC20 increased to 0.73 (%SEM 1.4) microgram/ml on placebo and 0.30 (%SEM 1.8) microgram/ml on flurbiprofen (p = 0.026). These results suggest that LTD4 released in asthmatic airways as a result of exercise stimulates inhibitory prostaglandin release, resulting in exercise refractoriness.
P J Manning; R M Watson; P M O'Byrne
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American review of respiratory disease     Volume:  148     ISSN:  0003-0805     ISO Abbreviation:  Am. Rev. Respir. Dis.     Publication Date:  1993 Oct 
Date Detail:
Created Date:  1993-11-15     Completed Date:  1993-11-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370523     Medline TA:  Am Rev Respir Dis     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  950-4     Citation Subset:  AIM; IM    
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
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MeSH Terms
Asthma, Exercise-Induced / drug therapy,  etiology*,  physiopathology
Bronchoconstriction / drug effects,  physiology
Double-Blind Method
Exercise Test
Flurbiprofen / therapeutic use
Forced Expiratory Volume / drug effects
Leukotriene D4 / administration & dosage,  physiology*
Middle Aged
Prostaglandins / physiology*
Tachyphylaxis / physiology
Reg. No./Substance:
0/Aerosols; 0/Prostaglandins; 5104-49-4/Flurbiprofen; 73836-78-9/Leukotriene D4

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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