Changes in neurokinin A (NKA) airway responsiveness with inhaled frusemide in asthma

Inhaled frusemide exerts a protective effect against bronchoconstriction induced by several indirect stimuli in asthma which could be due to interference of airway nerves. A randomised, double blind, placebo controlled study was performed to investigate the effect of the potent loop diuretic, frusemide, administered by inhalation on the bronchoconstrictor response to neurokinin A (NKA) and histamine in 11 asthmatic subjects.

Subjects attended the laboratory on four separate occasions to receive nebulised frusemide (40 mg) or matched placebo 10 minutes prior to bronchial challenge with NKA and histamine in a randomised, double blind order. Changes in airway calibre were followed as forced expiratory volume in one second (FEV1) and responsiveness to the agonists was expressed as the provocative concentration causing a 20% fall in FEV1 from baseline (PC20).

Compared with placebo, inhaled frusemide reduced the airway responsiveness to NKA in all the subjects studied, the geometric mean (range) values for PC20NKA increasing significantly (p < 0.001) from 130.3 (35.8-378.8) to 419.9 (126.5-1000) micrograms/ml after placebo and frusemide, respectively. Moreover, a small but significant change in airway responsiveness to histamine was recorded after frusemide, their geometric mean (range) PC20 values being 0.58 (0.12-3.80) and 1.04 (0.28-4.33) mg/ml after placebo and frusemide, respectively.

The decrease in airway responsiveness to NKA after administration of frusemide by inhalation suggests that this drug may interfere with the activation of neurotransmission in human asthma.