Inhaled frusemide and exercise induced asthma: evidence of a role for inhibitory prostanoids.
BACKGROUND
Inhaled frusemide protects subjects with asthma against a wide range of bronchoconstrictor challenges, including allergen, exercise and inhaled sodium metabisulphite. An investigation was designed to determine whether this protection is related to the production of inhibitory prostaglandins, such as prostaglandin E2 (PGE2), by studying the effect of the cyclooxygenase inhibitor indomethacin on the protection afforded by inhaled frusemide against exercise induced asthma.


METHODS
In a double blind crossover study 10 subjects with mild asthma were pretreated with indomethacin (50 mg thrice daily) or placebo capsules for three days; they then inhaled frusemide (40 mg) or placebo 10 minutes before an exercise test previously shown to cause a 20-30% fall in forced expiratory volume in one second (FEV1).


RESULTS
After inhalation of placebo exercise caused a similar maximum fall in FEV1 whether pretreatment was with placebo (26%) or indomethacin (25.2%). After inhalation of frusemide the maximum fall in FEV1 was reduced to 14.3% after placebo pretreatment and to 21.8% after indomethacin pretreatment; the difference between placebo and indomethacin pretreatment was significant (mean difference 7.5%, 95% limits 0.6%, 14.4%). The inhibitory effect of frusemide on the response to exercise, assessed as change in FEV1 over 30 minutes, was significantly greater with placebo (62%) than indomethacin (13%) pretreatment.


CONCLUSIONS
These findings support a role for inhibitory prostanoids, such as PGE2, in the beneficial effects of frusemide as a protection against exercise induced asthma.
Pavord
I D
ID
Respiratory Medicine Unit, City Hospital, Nottingham.
Wisniewski
A
A
Tattersfield
A E
AE
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D001250:Asthma, Exercise-Induced / Q000503:physiopathology / Q000517:prevention & control*; D004311:Double-Blind Method; D005080:Exercise Test; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D005665:Furosemide / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged
D005665:Furosemide; D007213:Indomethacin