Background: No consistent data are available regarding the effect of inhaled corticosteroids (ICS) in α1-antitrypsin-deficiency (AATD)-related COPD. Recent data report inflammatory effects of the polymers of α1-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 μm, 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 μg b.i.d., salmeterol 50 μg b.i.d. and oxitropium bromide 200 μg t.i.d. or (2) placebo, salmeterol 50 μg b.i.d. and oxitropium bromide 200 μg 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 FEV1, 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 FEV1, FVC, IC, ΔMEF50% 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.
- α-antitrypsin deficiency
- Chronic obstructive pulmonary disease
- Inhaled corticosteroids
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine