title: Acetazolamide and furosemide attenuate asthma induced by hyperventilation of cold, dry air.
abstract: We investigated the assumption that the efficacy of inhaled diuretics in asthma is dependent upon inhibition of the Na+/K+/2Cl- cotransporter. We compared the protective effect of acetazolamide, a diuretic without significant effect on the loop cotransporter, with the protection provided by inhaled furosemide in a cold, dry air hyperventilation model of asthma. Seven asthmatic subjects underwent a baseline bronchial challenge and then received a nebulized dose of 80 mg of furosemide or 500 mg of acetazolamide or saline placebo in a randomized, double-blind, placebo-controlled crossover design. Repeat challenges were performed immediately and at 2 and 4 h postnebulization. Acetazolamide caused a 47.2% increase in the amount of cold, dry air required to reduce the FEV1, by 20% (expressed in terms of respiratory heat loss as PD20RHL), from 0.79 multiplied or divided by (x/divided by) 1.13 kcal/min (geometric mean x/divided by geometric SEM) at baseline to 1.17 x/divided by 1.09 kcal/min postnebulization (p < 0.025). Furosemide increased the geometric mean PD20RHL by 53.9%, from 0.86 x/divided by 1.12 kcal/min to 1.33 x/divided by 1.12 kcal/min (p < 0.001). There was no significant change after placebo inhalation (0.81 x/divided by 1.15 kcal/min versus 0.87 x/divided by 1.10 kcal/min, NS). Airway responsiveness had returned to baseline by 2 h postnebulization on all 3 days. Furosemide also caused bronchodilatation, producing a 14.1% rise in the mean FEV1 (p < 0.005 versus prenebulization), whereas neither acetazolamide nor placebo altered airway tone significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Pulmonary and Critical Care Division, Beth Israel Hospital, Boston, MA 02215.
authors.forename: W J
authors.initials: WJ
authors.lastname: O'Donnell
authors.forename: M
authors.initials: M
authors.lastname: Rosenberg
authors.forename: R W
authors.initials: RW
authors.lastname: Niven
authors.forename: J M
authors.initials: JM
authors.lastname: Drazen
authors.forename: E
authors.initials: E
authors.lastname: Israel
mesh_terms: D000086:Acetazolamide / Q000008:administration & dosage / Q000627:therapeutic use*; D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D003080:Cold Temperature / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D005665:Furosemide / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D006813:Humidity; D006985:Hyperventilation / Q000150:complications; D008297:Male; D014556:Urine
chemical_list: D005665:Furosemide; D000086:Acetazolamide