title: New developments in the treatment of COPD: comparing the effects of inhaled corticosteroids and N-acetylcysteine.
abstract: Inhaled corticosteroids (ICS) are widely used for the treatment of COPD despite of controversial statements concerning their efficacy. The use of N-acetylcysteine (NAC), a mucolytic drug with antioxidant properties, is less clear, but it may counteract the oxidant-antioxidant imbalance in COPD. The aim of this study was to evaluate whether treatment of COPD patients with ICS or NAC is able to improve inflammatory indices and to enhance lung function. ICS treatment enhanced protective markers for oxidative stress such as glutathione peroxidase (GPx) (51.2 +/-5.8 vs. 62.2 +/-8.6 U/g Hb, P<0.02) and trolox-equivalent antioxidant capacity (TEAC) (1.44 +/-0.05 vs. 1.52 +/-0.06 mM, P<0.05). NAC decreased sputum eosinophil cationic protein (318 +/-73 vs. 163 +/-30 ng/ml, P<0.01) and sputum IL-8 (429 +/-80 vs. 347 +/-70 ng/ml, P<0.05). The increased antioxidant capacity prevented an up-regulation of adhesion molecules, since the levels of intracellular adhesion molecule 1 (ICAM-1) correlated negatively with GPx (P<0.0001) and TEAC (P<0.0001). On the other hand, expression of adhesion molecules was promoted by inflammation, reflected by a positive correlation between the levels of IL-8 and ICAM-1 (P<0.0001). The effects of treatment on lung function were only reflected in the FEV(1) values. The absolute value of FEV(1), both before and after salbutamol inhalation, increased from 1690 +/-98 to 1764 +/-110 ml, and 1818 +/-106 to 1906 +/-116 ml, respectively, after ICS (P<0.05) . Ten weeks after treatment, FEV(1) values dropped to 1716 +/-120 ml post-salbutamol (P<0.05). When followed by treatment with NAC, these values decreased even further to 1666 +/-84 ml. These results suggest that ICS improved lung function in COPD patients with moderate airflow obstruction, beside a minor improvement in the oxidant-antioxidant imbalance leading to a lesser expression of ICAM-1. Treatment with NAC decreased some inflammatory parameters and had indirectly an inhibitory effect on the expression of adhesion molecules.
authors.affiliation: Department of Respiratory Medicine, Antwerp University, Antwerp, Belgium. frans.vanoverveld@pmintl.com
authors.forename: F J
authors.initials: FJ
authors.lastname: van Overveld
authors.forename: U
authors.initials: U
authors.lastname: Demkow
authors.forename: D
authors.initials: D
authors.lastname: Górecka
authors.forename: W A
authors.initials: WA
authors.lastname: de Backer
authors.forename: J
authors.initials: J
authors.lastname: Zielinski
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage*; D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000975:Antioxidants / Q000008:administration & dosage*; D004311:Double-Blind Method; D047150:Eosinophil Cationic Protein / Q000097:blood / Q000378:metabolism; D005100:Expectorants / Q000008:administration & dosage*; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000097:blood; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000378:metabolism; D016209:Interleukin-8 / Q000097:blood / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D012129:Respiratory Function Tests; D013183:Sputum / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D005100:Expectorants; D016209:Interleukin-8; D018799:Intercellular Adhesion Molecule-1; D000068298:Fluticasone; D005979:Glutathione Peroxidase; D047150:Eosinophil Cationic Protein; C479220:RNASE3 protein, human; D000111:Acetylcysteine