Inhibition of sodium metabisulphite induced bronchoconstriction by frusemide in asthma: role of cyclooxygenase products.
BACKGROUND
Inhaled frusemide inhibits airway responses to sodium metabisulphite and other indirect bronchial challenges in asthma by undetermined mechanisms which may relate to its ability to stimulate prostaglandin release. Inhalation of sodium metabisulphite provokes indirect bronchoconstriction, possibly by activating sensory nerves. To investigate the role of cyclooxygenase products in the airway actions of frusemide and sodium metabisulphite, the effects of a potent cyclooxygenase inhibitor, flurbiprofen, alone and in combination with frusemide were investigated against airway responsiveness to sodium metabisulphite.


METHODS
In a double blind double placebo controlled study, 12 mild asthmatic subjects attended on four occasions to undergo three inhalation challenges with sodium metabisulphite. A baseline challenge was performed one hour before oral intake of flurbiprofen 200 mg or matched placebo, and two hours before inhalation of frusemide 40 mg or matched placebo. A second challenge was performed immediately after inhalation of frusemide (two hours after flurbiprofen) with a further challenge three hours later. The log concentration provoking a 20% fall in FEV1 (log PC20) was used to assess airway responsiveness to sodium metabisulphite.


RESULTS
Frusemide caused an immediate 1.9 doubling dose protection and a lesser 0.7 doubling dose protection at three hours. This protection was enhanced by flurbiprofen at both time points to 2.7 (early) and 1.9 (late) doubling doses. In addition, flurbiprofen alone significantly reduced airway responsiveness to sodium metabisulphite by 1.1 doubling doses at both two and five hours.


CONCLUSIONS
The generation of bronchoprotective prostaglandins is unlikely to underlie the inhibitory action of frusemide against airway responsiveness to sodium metabisulphite. Endogenous contractile prostaglandins within the airways may be involved in the bronchoconstrictor response to sodium metabisulphite.
O'Connor
B J
BJ
Department of Thoracic Medicine, National Heart and Lung Institute, Royal Brompton National Heart and Lung Hospitals, London.
Barnes
P J
PJ
Chung
K F
KF
D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005480:Flurbiprofen / Q000627:therapeutic use*; D005665:Furosemide / Q000627:therapeutic use*; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008297:Male; D013447:Sulfites / Q000037:antagonists & inhibitors*
D016861:Cyclooxygenase Inhibitors; D013447:Sulfites; D005480:Flurbiprofen; C030981:metabisulfite; D005665:Furosemide