title: Refractoriness to inhaled sodium metabisulphite in subjects with mild asthma.
abstract: Refractoriness occurs after challenges causing mediator release in asthma, by a mechanism which may involve inhibitory prostaglandins. Bronchoconstriction due to inhaled sodium metabisulphite is thought to involve neural pathways and to be independent of mediator release; whether it shows refractoriness is uncertain. We have sought evidence of refractoriness to the bronchoconstrictor response to inhaled sodium metabisulphite in subjects with mild asthma, and have tested the hypothesis that the development of refractoriness involves inhibitory prostaglandins. Twelve subjects were challenged twice with a dose of sodium metabisulphite, previously shown to cause a 20% fall in forced expiratory volume in one second (FEV1); the second challenge proceeded after recovery from the first. The response to sodium metabisulphite was expressed as the maximum % fall in FEV1 and area under the change in FEV1 curve over 20 min (AUC). Nine subjects were studied after double-blind treatment with oral indomethacin, 50 mg t.d.s., or placebo, for 3 days. The second sodium metabisulphite challenge caused significantly less bronchoconstriction than the first (mean maximum fall in FEV1 13.1 and 24.3%, respectively). Nine subjects showed a greater than 50% reduction in the response to the second challenge (mean reduction in AUC 73.7%). In these subjects, indomethacin did not alter the response to the first sodium metabisulphite challenge, or the mean maximum fall in FEV1 in response to the second challenge (placebo 9.7%, indomethacin 11.2%), but significantly increased the AUC of the second challenge (placebo 55, indomethacin 114). The mean reduction in AUC from first to second challenge was 78% with placebo and 48% with indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Respiratory Medicine Unit, City Hospital, Nottingham, UK.
authors.forename: I D
authors.initials: ID
authors.lastname: Pavord
authors.forename: A
authors.initials: A
authors.lastname: Wisniewski
authors.forename: A E
authors.initials: AE
authors.lastname: Tattersfield
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects; D004311:Double-Blind Method; D004351:Drug Resistance; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011453:Prostaglandins / Q000502:physiology*; D013447:Sulfites / Q000008:administration & dosage
chemical_list: D011453:Prostaglandins; D013447:Sulfites; C005200:sodium metabisulfite; D007213:Indomethacin