title: An open study of auranofin in the treatment of steroid-dependent asthma.
abstract: To determine the efficacy of oral gold in asthma, 20 patients with steroid-dependent asthma received auranofin at a dose of 3 mg by mouth, twice daily, in a 24-week open clinical trial. Prospective evaluation of bronchial responsiveness to methacholine was determined before and 8 and 16 weeks after initiation of auranofin therapy. Serial spirometry (FEV1 and FVC), lung volumes, and diffusing capacities (single breath carbon monoxide diffusing capacity of the lungs) were measured before and at 10 and 20 weeks after treatment. All subjects were required to record concomitant medications, symptom scores, and morning and evening peak expiratory flow rates. In vitro immunologic studies performed before and after 8 and 20 weeks of auranofin therapy included leukocyte histamine release in response to antihuman IgE, lymphocyte blast transformation in response to concanavalin A and phytohemagglutinin, and leukocyte inhibitory factor activity in response to Candida albicans and tetanus toxoid antigens. In 18 patients evaluated, there were no significant differences between baseline and posttreatment spirometry, single breath carbon monoxide diffusing capacity of the lungs, and lung volumes. At week 16 of treatment, the steroid cumulative dose or the total prednisone dose administered from 7 days before through 10 days after each methacholine test day decreased from a mean of 293 +/- 125 mg at baseline to 192 +/- 115 mg. At week 16, nine of 18 patients (50%) exhibited decreased methacholine responsiveness as defined by a more than one-half log10 increase in the concentration of methacholine causing a 20% decrease in FEV1. A significant correlation (r = 0.60) was observed between the increase in the concentration of methacholine causing a 20% decrease in FEV1 and the decrease in steroid cumulative dose after 16 weeks of treatment. Leukocyte histamine release to anti-IgE exhibited significant reductions from baseline at week 20 to 10(-2) (p less than 0.002) and at 10(-3) (p less than 0.005) dilutions. At week 20, leukocyte inhibitory factor activity in response to Candida increased from baseline at the 0.1 mg per well (p = 0.025) and 1 mg per well (p = 0.05) concentrations; similarly, the responses to tetanus toxoid increased at the 1 mg per well (p less than 0.05) and 0.1 mg per well (p less than 0.01) concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Medicine, University of Cincinnati Medical Center, OH 45267.
authors.forename: D I
authors.initials: DI
authors.lastname: Bernstein
authors.forename: I L
authors.initials: IL
authors.lastname: Bernstein
authors.forename: S S
authors.initials: SS
authors.lastname: Bodenheimer
authors.forename: R G
authors.initials: RG
authors.lastname: Pietrusko
mesh_terms: D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001310:Auranofin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D012129:Respiratory Function Tests; D012871:Skin Diseases / Q000139:chemically induced
chemical_list: D008688:Methacholine Compounds; D016210:Methacholine Chloride; D001310:Auranofin; D011241:Prednisone