title: Effects of inhaled furosemide on platelet-activating factor challenge in mild asthma.
abstract: Furosemide (Fur) may have an anti-inflammatory effect on airways in patients with asthma although its intrinsic mechanism remains elusive. Platelet-activating factor (PAF) is a potent proinflammatory mediator that induces systemic and respiratory effects in normal control subjects and asthmatics. The 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 (forced expiratory volume in one second, 95+/-4%) in a randomized, double-blind, placebo-controlled, cross-over fashion, one week apart. PAF challenge (18 microg) was carried out 15 min after administration of Fur or placebo. Peripheral blood neutrophils, respiratory system resistance, and arterial blood gases were measured at baseline, and 5, 15 and 45 min after PAF; urinary cysteinyl leukotriene E4 (uLTE4) was also measured, at baseline and 120 min 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 after PAF inhalation. It is concluded that furosemide is not effective in protecting against platelet-activating factor challenge in patients with asthma despite its potential inhibition of leukotriene synthesis. These findings reinforce the view that the pulmonary effects of platelet-activating factor are mediated through different pathways.
authors.affiliation: Dept de Medicina, Institut d'Investigacions Biomédiques August Pi i Sunyer, Hospital Clinic, Universitat de Barcelona, Spain.
authors.forename: A L
authors.initials: AL
authors.lastname: Echazarreta
authors.forename: F P
authors.initials: FP
authors.lastname: Gómez
authors.forename: J
authors.initials: J
authors.lastname: Ribas
authors.forename: M
authors.initials: M
authors.lastname: Achaval
authors.forename: J A
authors.initials: JA
authors.lastname: Barberà
authors.forename: J
authors.initials: J
authors.lastname: Roca
authors.forename: K F
authors.initials: KF
authors.lastname: Chung
authors.forename: R
authors.initials: R
authors.lastname: Rodriguez-Roisin
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000403:Airway Resistance; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D001784:Blood Gas Analysis; D016084:Bronchoconstriction / Q000187:drug effects*; D003404:Creatinine / Q000652:urine; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D005665:Furosemide / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007958:Leukocyte Count; D017999:Leukotriene E4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000652:urine; D008297:Male; D009330:Nebulizers and Vaporizers; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011659:Pulmonary Gas Exchange / Q000187:drug effects*
chemical_list: D010972:Platelet Activating Factor; D017999:Leukotriene E4; D005665:Furosemide; D003404:Creatinine