EFFECT OF INHALED FRUSEMIDE AND ORAL INDOMETHACIN ON THE AIRWAY RESPONSE TO HYPERTONIC SALINE CHALLENGE IN ASTHMATIC SUBJECTS

Background - Inhaled frusemide inhibits airway narrowing and causes a transient increase in forced expiratory volume in one second (FEV(1)) during hypertonic saline challenge. This inhibitory effect could be se condary to prostaglandin release during challenge. The involvement of prostaglandins in the inhibitory action of frusemide during challenge with 4.5% NaCl was investigated by premedicating with indomethacin, a prostaglandin synthetase inhibitor. Methods - Fourteen asthmatic subje cts (eight women) aged 26.6 (range 18-56) years participated in a doub le blind, placebo controlled, crossover study. The subjects attended f ive times and inhaled 4.5% NaCl for 0.5, 0.75, 1, 1.5, 2, 4, 8, 8, and 8 minutes, or part thereof, or until a provocative dose causing a 20% fall in FEV(1) (PD20 FEV(1)) was recorded. Indomethacin (100 mg/day) or placebo were taken three days before all visits, except control day . The FEV(1) was measured and frusemide (38.0 (6.4) mg, pH=9) or vehic le (0.9% NaCl, pH=9) were inhaled 10 minutes before the challenge. Bro nchodilation was calculated as the percentage rise in FEV(1) from the prechallenge FEV(1) to the highest FEV(1) recorded during the challeng e. Results - Frusemide caused a fold increase in PD20 FEV(1) compared with the vehicle which was similar in the presence of both indomethaci n and placebo (3.7 (95% CI 2.0 to 7.3) versus 3.3 (2.0 to 5.4)). Fruse mide, but not vehicle, also caused a transient percentage rise in FEV( 1) during challenge with 4.5% NaCl which was not blocked by indomethac in (3.6% (1.2 to 6.0)) or placebo (3.1% (1.0 to 5.2)). Conclusions - I nhaled frusemide inhibited airway narrowing and caused a transient inc rease in FEV(1) during challenge with 4.5% NaCl. These effects were no t blocked by indomethacin, which suggests that the inhibitory action o f frusemide is not secondary to prostaglandin release.