Protective Effect of Inhaled Furosemide on Allergen-Induced Early and Late Asthmatic Reactions

Abstract

The movement of ions and water across the membranes of bronchial cells is part of the control of the bronchial obstructive response to physical stimuli. In a double-blind, randomized, crossover study, we compared the effect of an aerosol of the loop diuretic furosemide with that of a placebo on the early (within 60 minutes) and late (4 to 12 hours) asthmatic responses to a specific inhaled allergen. We studied 11 subjects with mild allergic asthma, who had both early and late asthmatic responses to a specific inhaled allergen in a preliminary challenge. After placebo administration, the maximal changes (mean +/- SE) from base line in the forced expiratory volume in one second (FEV1) and specific airway resistance were, respectively, a decrease of 35 +/- 4 percent and an increase of 288 +/- 56 percent between 0 and 60 minutes after inhalation of the allergen (early response) and a decrease of 35 +/- 5 percent and an increase of 301 +/- 40 percent between 4 and 12 hours (late response). After furosemide administration (4 ml; 10 mg per milliliter), the early response to inhaled allergen was markedly attenuated in all the subjects, and the late response in all but one. The maximal changes in the FEV1 and specific airway resistance were, respectively, a decrease of 11 +/- 2 percent and an increase of 61 +/- 2 percent between 0 and 60 minutes and a decrease of 20 +/- 4 percent and an increase of 178 +/- 25 percent between 4 and 12 hours (P less than 0.05 for all comparisons). No significant differences were seen in the bronchoconstrictor response to inhaled methacholine after furosemide or placebo administration. We conclude that a furosemide-sensitive mechanism in the airways is involved in the pathogenesis of the reactions of patients with allergic asthma. Whether inhaled furosemide might be useful in the treatment of allergic asthma is uncertain and will require further study.

Inhaled frusemide does not affect lung mucociliary clearance in healthy and asthmatic subjects

“…Frusemide has been shown to have the capacity to prevent the release of inflammatory mediators, such as leukotrienes, from passively-sensitized human lung in vitro [23]. However, we found no evidence that frusemide was active in reversing the reduced clearance observed in asthmatic patients, even at a dose that is known to inhibit allergen-induced acute response in asthmatics [1,24]. Studies of the protective effect of frusemide against airway challenges have been performed within 30 min of challenge, but in a study of its inhibitory effect against cough challenges, we found an effect lasting for up to 3 h [25].…”

“…There were no statistically significant differences between the two runs for FEV 1 and Vmax 50 within each group. Alveolar deposition for the placebo and frusemide were 44±4 vs 45±3%, respectively, for the asthmatic group; and 66±7 vs 57±9% respectively, for the healthy group.…”

“…Inhaled frusemide inhibits the bronchoconstrictor effects of indirect challenges, such as allergens, distilled water, sodium metabisulphite and adenosine, in asthmatic patients [1][2][3][4]. Because frusemide has no effect against the bronchoconstriction induced by methacholine and histamine [3,4], it is likely that it has no direct effect on airway smooth muscle, and that the effect of frusemide is to inhibit the release of mediators induced by indirect challenges [5].…”

The Airways: A Promising Route for the Pulmonary Delivery of Anticancer Agents

“…Inhaled furosemide was used with some success to treat breathlessness asthma patients and healthy volunteers whose breathlessness was induced (Bianco et al, 1989, Nishino et al, 2000. This finding led to inhaled furosemide being evaluated in cancer patients.…”

Time-limited protective effect of inhaled frusemide against aspirin-induced bronchoconstriction in aspirin-sensitive asthmatics

“…Eur Respir J., 1994Respir J., , 7, 1825Respir J., -1829 Inhalation of frusemide and, to a lesser extent other loop diuretics, inhibits the bronchoconstriction induced by allergens and by several nonallergic stimuli, such as exercise, hypo-and hypertonic aerosols, cold air, metabisulphite and adenosine [1,2]. Although frusemide protects against the late asthmatic reaction up to 12 h after allergen exposure [3], the protective effect against ultrasonically-nebulized distilled water and sodium metabisulphite is relatively short-lived, lasting for 1-2 h [4,5]. Bronchoconstriction induced by inhaled acetylsalicylic acid (ASA) in aspirin-sensitive asthmaticshas a relatively long time course, peaking around the second hour and usually lasting more than 4 h after exposure [6,7].…”