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) st 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 acetazoiamide nor placebo altered airway tone significantly. In addition, urine output in the 4 h after nebulization increased from a mean of 270 +/- 120 ml postplacebo to 690 +/- 170 ml after acetazolamide (0.05 < p < 0.10) and 1,350 +/- 200 ml after furosemide administration (p < 0.025 versus acetazolamide and p < 0.005 versus placebo); both drugs affected urinary pH. These results demonstrate that acetazolamide, a diuretic lacking loop diuretic activity, can inhibit experimental asthma. This finding suggests that an inhaled diuretic need not inhibit the loop diuretic-sensitive Na+/K+/2Cl- cotransporter In order to attenuate the asthmatic response to a bronchoconstrictor stimulus.