Acetazolamide and furosemide attenuate asthma induced by hyperventilation of cold, dry air.
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)
O'Donnell
W J
WJ
Pulmonary and Critical Care Division, Beth Israel Hospital, Boston, MA 02215.
Rosenberg
M
M
Niven
R W
RW
Drazen
J M
JM
Israel
E
E
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
D005665:Furosemide; D000086:Acetazolamide