Am. J. Respir. Crit. Care Med., Vol 152, No. 2, Aug 1995, 625-628.
Inhaled indomethacin prevents bronchoconstrictive response to distilled water but not to histamine in children with asthma
T Shimizu, H Mochizuki, S Maeda, M Shigeta, A Morikawa and T Kuroume
Department of Pediatrics, Gunma University School of Medicine, Japan.
We evaluated the effect of inhaled indomethacin, a nonsteroidal
antiinflammatory drug (NSAID), against bronchoconstriction induced by
ultrasonically nebulized distilled water (UNDW) in children with asthma.
Ten children with asthma (eight males and two females, with a mean +/- SEM
age of 10.7 +/- 0.7 yr), who had a decrease in FEV1 of at least 20% after
UNDW inhalation, were enrolled in this study. These subjects were
pretreated with inhaled indomethacin (3 mg/m2 body- surface area) or
placebo (0.9% saline) according to a single-blind, randomized, crossover
design, and underwent a UNDW challenge test 15 min after the pretreatment.
Furthermore, to study the possibility that indomethacin has a direct effect
on airway smooth muscle, bronchial provocation with histamine was performed
in seven subjects on two further days after pretreatment with indomethacin
or placebo. Inhaled indomethacin had no effect on baseline pulmonary
function, but did prevent the UNDW-induced decline in FEV1 (p < 0.01).
Inhaled indomethacin did not modify the bronchoconstrictor response to
histamine, indicating that a direct effect of this agent on airway smooth
muscle is unlikely. The inhibition of local prostaglandin synthesis in the
airways may be involved in the effect of indomethacin.
