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

Abstract

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.

• Authors: Luciano Corda, Enrica Bertella, Giuseppe Emanuele La Piana, Enrico Boni, Stefania Redolfi, Claudio Tantucci
• Journal: Respiration; international review of thoracic diseases (Respiration) Vol. 76 Issue 1 Pg. 61-8 ( 2008) ISSN: 1423-0356 [Electronic] Switzerland
• PMID: 18319586 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: 2008 S. Karger AG, Basel.

Chemical References

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

Topics

• Administration, Inhalation
• Aged
• Albuterol (administration & dosage, 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, drug therapy, physiopathology)
• Respiratory Function Tests
• Salmeterol Xinafoate
• Scopolamine Derivatives (administration & dosage)
• alpha 1-Antitrypsin Deficiency (complications)