Time-limited p protective e effect o of iinhaled ffrusemide a against aspirin-induced b bronchoconstriction iin a aspirin-sensitive asthmatics

Time-limited protective effect of inhaled frusemide against aspirin-induced bronchocon- striction in aspirin-sensitive asthmatics. P. Sestini, M.G. Pieroni, R.M. Refini, M. Robuschi, G. Gambaro, S. Spagnotto, A. Vaghi, S. Bianco. ERS Journals Ltd 1994. ABSTRACT: Inhaled frusemide effectively prevents the bronchial obstructive response to allergens and to a number of nonallergic stimuli. In most of the ex- perimental models in which it has been tested, the protective effect of frusemide has been evaluated for only a short time after administration. In aspirin-sensitive patients, acetylsalicylic acid causes an asthmatic reaction which typically lasts for 2 h or more after exposure. We investigated the presence and duration of the protective effect of inhaled frusemide against the bronchial response to aspirin in sensitive patients, using a specific inhalation challenge with lysine acetylsalicylate (LASA). In the first study, eight subjects with aspirin-asthma underwent two bronchial challenges with a single dose of lysine acetylsalicylate administered through a jet nebulizer, after treatment with 40 mg inhaled frusemide or placebo, according to a randomized, double-blind protocol. Forced expiratory volume in one second (FEV 1 ) was monitored for 120 min after challenge. In the second study in eight patients, the protocol was modified by the use of a dosimeter for delivery of lysine acetylsalicylate, by reducing the dose of lysine acetylsalicylate to avoid intense reactions, and by extending the follow-up to 4 h. In the first study, after placebo, FEV 1 gradually decreased, reaching a maxi- mum decrement of 39±3% at 120min. Inhaled frusemide exerted a significant protection at all time-points, although this activity appeared to decrease with time. In the second study, after placebo, inhaled lysine acetylsalicylate caused a gradual decrease in FEV 1 , which reached a maximum decrement at 180 min. Frusemide provided a significant protection in the first 90 min of the reaction; thereafter, FEV 1 fell gradually to levels similar to placebo. We conclude that inhaled frusemide effectively prevents the asthmatic reaction to lysine acetylsalicylate in aspirin sensitive patients, but this protective effect is limited in time.