POTENTIATION OF THE ANTIREACTIVE, ANTIASTHMATIC EFFECT OF INHALED FUROSEMIDE BY INHALED LYSINE ACETYLSALICYLATE

Nonsteroid antiinflammatory drugs interfere with the diuretic activity of furosemide, implying that this effect is at least partially depend ent on renal prostaglandin synthesis. To investigate whether prostagla ndin production could also modulate the bronchial antireactive activit y of this diuretic drug, we investigated the effect of inhaled lysine acetylsalicylate (162 mg) and of furosemide (18 mg), alone and in comb ination, on the bronchial obstructive response to ultrasonically nebul ized water in asthmatic patients. The study was also prompted by the c onflicting results obtained in previous studies of oral nonsteroid ant iinflammatory drugs. Fifteen asthmatic patients underwent bronchial ch allenge with a mist of ultrasonically nebulized distilled water at the same time of day on four occasions, 2-4 days apart, 15 min after prem edication according to a double-blind, randomized protocol. After plac ebo, mean PD15 to water mist did not differ from a preliminary test (2 .1 +/- 0.2 and 2.5 +/- 0.4 ml, M +/- SE, respectively). After lysine a cetylsalicylate, mean PD15 rose to 5.0 +/- 0.7 ml (2.8 +/- 0.6 times h igher than placebo); after furosemide, to 9.0 +/- 1.5 ml (4.4 +/- 0.9 times over placebo); and after the two drugs in combination, to 32.2 /- 5.6 ml (16.3 +/- 3.0 times higher than placebo). Similar results we re obtained with inhaled indomethacin, whereas sodium salicylate had n o effect. These data indicate that the bronchial antireactive activity of inhaled furosemide is greatly enhanced by inhaled lysine acetylsal icylate through a mechanism which probably involves inhibition of the local synthesis of prostaglandins, and could have therapeutic implicat ions.