Inhaled corticosteroids as additional treatment in alpha-1-antitrypsin-deficiency-related COPD

Respiration. 2008;76(1):61-8. doi: 10.1159/000119718. Epub 2008 Mar 4.


Background: No consistent data are available regarding the effect of inhaled corticosteroids (ICS) in alpha(1)-antitrypsin-deficiency (AATD)-related COPD. Recent data report inflammatory effects of the polymers of alpha(1)-antitrypsin on the peripheral lung.

Objectives: The aim of this study was to assess the effectiveness of an extra-fine ICS, hydrofluoroalkane-134a beclometasone dipropionate (HFA-BDP) with a mass median aerodynamic diameter of 1.1 microm, on lung function and exercise tolerance in COPD patients with AATD when added to long-acting bronchodilators (LABAs).

Methods: After a 1-week washout, 8 steroid-naïve COPD patients with AATD (ZZ genotype), within a double-blind randomized cross-over study, were assigned to one of the following 16-week treatments: (1) HFA-BDP 400 microg b.i.d., salmeterol 50 microg b.i.d. and oxitropium bromide 200 microg t.i.d. or (2) placebo, salmeterol 50 microg b.i.d. and oxitropium bromide 200 microg t.i.d; after a 2-week washout period they received the other treatment. In weeks 1, 17, 19 and 35, patients took a spirometry assessment (breathing air and heliox) and a shuttle walking test (SWT) with dyspnea assessed by the modified Borg scale.

Results: Significant differences in improvement were found in FEV(1), FVC, IC, distance covered and dyspnea perceived during SWT between the 2 treatments and baseline values (p < 0.05; Friedman's test). However, further analysis showed that only the LABAs + ICS condition showed significant increases in the FEV(1), FVC, IC, DeltaMEF(50%) and distance covered during SWT along with a reduction in maximum isostep exertional dyspnea (p < 0.05; Wilcoxon test). A greater distance was walked at the end of the SWT with LABA + ICS than LABAs alone (301 +/- 105 vs. 270 +/- 112 m; p < 0.05).

Conclusions: In AATD-related COPD patients (ZZ genotype) the addition of extra-fine ICS to LABAs decreases airway narrowing, mostly in the small airways, further reducing dynamic hyperinflation with a marked improvement in exercise tolerance and dyspnea, suggesting that a peripheral inflammatory process contributes to airflow obstruction in these patients.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Aged
  • Albuterol / administration & dosage
  • Albuterol / analogs & derivatives
  • Beclomethasone / administration & dosage*
  • Bronchodilator Agents / administration & dosage*
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Therapy, Combination
  • Dyspnea
  • Exercise Tolerance
  • Female
  • Glucocorticoids / administration & dosage*
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / complications
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Respiratory Function Tests
  • Salmeterol Xinafoate
  • Scopolamine Derivatives / administration & dosage
  • alpha 1-Antitrypsin Deficiency / complications*


  • Bronchodilator Agents
  • Glucocorticoids
  • Scopolamine Derivatives
  • Salmeterol Xinafoate
  • oxitropium
  • Beclomethasone
  • Albuterol