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


OBJECTIVE
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.
Corda
Luciano
L
Prima Divisione di Medicina, Spedali Civili, Brescia, Italy. medicinarespiratoria@libero.it
Bertella
Enrica
E
La Piana
Giuseppe Emanuele
GE
Boni
Enrico
E
Redolfi
Stefania
S
Tantucci
Claudio
C
D000280:Administration, Inhalation; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives; D001507:Beclomethasone / Q000008:administration & dosage*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004417:Dyspnea; D017079:Exercise Tolerance; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D012129:Respiratory Function Tests; D000068299:Salmeterol Xinafoate; D012602:Scopolamine Derivatives / Q000008:administration & dosage; D019896:alpha 1-Antitrypsin Deficiency / Q000150:complications*
D001993:Bronchodilator Agents; D005938:Glucocorticoids; D012602:Scopolamine Derivatives; D000068299:Salmeterol Xinafoate; C017590:oxitropium; D001507:Beclomethasone; D000420:Albuterol