The bronchoconstriction caused by inhaled
neurokinin A (NKA) in patients with
asthma is indirect. The mediators involved in NKA-induced bronchoconstriction are unknown. Studies with various
H1 receptor antagonists were negative, making an important contribution of
histamine unlikely. To study the role of cysteinyl
leukotrienes in
neurokinin A-induced bronchoconstriction, we performed a randomised, double-blind, cross-over, placebo controlled trial in 12 patients with mild to moderate
asthma.
Zafirlukast and matching placebo were given orally, 40 mg the evening before and 40 mg the morning of assessment. In one period NKA was administered, in the other period
leukotriene D4 (
LTD4). Increasing concentrations of NKA and
LTD4 were inhaled from a 30 L bag, after nebulization via a Mallinckrodt nebuliser. The difference between log10PC20LTD4
after treatment with placebo or
zafirlukast was highly significant (p<0.0001). A trend was observed towards a difference between log10PC20
neurokinin A after treatment with placebo or
zafirlukast (p=0.0741). The dose ratio for the
neurokinin A provocation was 4.4 and for the
LTD4 provocation 67.7. In conclusion,
zafirlukast had a large inhibitory effect on LTD4-induced bronchoconstriction, but offered only limited protective effect against
neurokinin A-induced bronchoconstriction. We suggest that
leukotrienes play a limited role in the
bronchoconstrictor effect of
neurokinin A in patients with
asthma.