title: Short-term treatment with budesonide does not improve hyperresponsiveness to adenosine 5'-monophosphate in COPD.
abstract: The role of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease (COPD) is unclear. We investigated the effects of budesonide on airway hyperresponsiveness (AHR) to methacholine (MCh) and adenosine 5'-monophosphate (AMP), to which we hypothesized the existence of greater sensitivity. Additionally, we studied the effects of budesonide on terfenadine and ipratropium bromide and on serum levels of interleukin-8 (IL-8) and histamine. Forty-four hyperresponsive smokers with moderate to severe COPD participated in the study. MCh and AMP challenges were given on three study days, after pretreatment with single doses of ipratropium bromide, terfenadine, or placebo. Thereafter, subjects were randomized to 6 wk treatment with either 1,600 microg budesonide or placebo, and the same three study days were repeated. Budesonide, as compared with placebo, did not significantly change PC20AMP, PC20MCh, or FEV1 after placebo pretreatment. Budesonide increased PC20MCh after ipratropium bromide pretreatment, from 5.05 to 10.20 mg/ml (p = 0.036). Budesonide decreased serum IL-8 from 9.2 +/- 3.7 to 6.2 +/- 2.1 pg/ml (p < 0.001). We conclude that AMP did not elicit greater sensitivity than MCh in assessing short-term effects of budesonide on AHR in smokers with COPD. We suggest that long-term treatment with inhaled corticosteroids might be beneficial, by reducing neutrophil load in the airways and improving the action of anticholinergic drugs.
authors.affiliation: Department of Pulmonology, University Hospital Groningen, The Netherlands.
authors.forename: S R
authors.initials: SR
authors.lastname: Rutgers
authors.forename: G H
authors.initials: GH
authors.lastname: Koëter
authors.forename: T W
authors.initials: TW
authors.lastname: van der Mark
authors.forename: D S
authors.initials: DS
authors.lastname: Postma
mesh_terms: D000249:Adenosine Monophosphate; D000280:Administration, Inhalation; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use; D019819:Budesonide / Q000008:administration & dosage / Q000627:therapeutic use*; D018680:Cholinergic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006632:Histamine / Q000097:blood; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D009241:Ipratropium / Q000008:administration & dosage / Q000627:therapeutic use; D007958:Leukocyte Count / Q000187:drug effects; D008137:Longitudinal Studies; D008173:Lung Diseases, Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects; D010919:Placebos; D012907:Smoking / Q000503:physiopathology; D016593:Terfenadine / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D005938:Glucocorticoids; D006634:Histamine H1 Antagonists; D016209:Interleukin-8; D010919:Placebos; D016210:Methacholine Chloride; D000249:Adenosine Monophosphate; D019819:Budesonide; D016593:Terfenadine; D006632:Histamine; D009241:Ipratropium