Effects of inhaled furosemide on platelet-activating factor challenge in mild asthma

Furosemide (Fur) may have an anti-inflammatory effect on airways in patient s with asthma although its intrinsic mechanism remains elusive. Platelet-ac tivating factor (PAF) is a potent proinflammatory mediator that induces sys temic and respiratory effects in normal control subjects and asthmatics, Th e aim of this study was to assess whether pretreatment with nebulized Fur ( 40 mg) was able to modulate PAF-induced systemic and respiratory effects in asthma. Eleven patients were studied (mean+/-sem 22+/-0.8 yrs) with mild asthma (fo rced expiratory volume in one second, 95+/-4%) in a randomized, double-blin d, placebo-controlled, cross-over fashion, one week apart. PAF challenge (1 8 mu g) was carried out 15 min after administration of Fur or placebo. Peri pheral blood neutrophils, respiratory system resistance, and arterial blood gases were measured at baseline, and 5, 15 and 45 min after PAF; urinary c ysteinyl leukotriene E-4 (uLTE(4)) was also measured, at baseline and 120 m in after PAF challenge. Although Fur did not alter PAF-induced systemic and respiratory effects, it did partially inhibit (63%; p<0.04) the increments of uLTE4 levels shown a fter PAF inhalation. It is concluded that furosemide is not effective in protecting against plat elet-activating factor challenge in patients,vith asthma despite its potent ial inhibition of leukotriene synthesis. These findings reinforce the view that the pulmonary effects of platelet-activating factor are mediated throu gh different pathways.