title: Inhaled indomethacin prevents bronchoconstrictive response to distilled water but not to histamine in children with asthma.
abstract: 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.
authors.affiliation: Department of Pediatrics, Gunma University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shimizu
authors.forename: H
authors.initials: H
authors.lastname: Mochizuki
authors.forename: S
authors.initials: S
authors.lastname: Maeda
authors.forename: M
authors.initials: M
authors.lastname: Shigeta
authors.forename: A
authors.initials: A
authors.lastname: Morikawa
authors.forename: T
authors.initials: T
authors.lastname: Kuroume
mesh_terms: D000280:Administration, Inhalation; D001249:Asthma / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D002648:Child; D018592:Cross-Over Studies; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006632:Histamine / Q000008:administration & dosage; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D009330:Nebulizers and Vaporizers; D010919:Placebos; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D016037:Single-Blind Method; D014465:Ultrasonics; D014867:Water / Q000008:administration & dosage
chemical_list: D010919:Placebos; D011448:Prostaglandin Antagonists; D014867:Water; D006632:Histamine; D007213:Indomethacin