INIMEC - CONICET   05467
INSTITUTO DE INVESTIGACION MEDICA MERCEDES Y MARTIN FERREYRA
Unidad Ejecutora - UE
artículos
Título:
Effects of Aclidinium Bromide in a Cigarette Smoke?Exposed Guinea Pig Model of Chronic Obstructive Pulmonary Disease
Autor/es:
DAVID DOMINGUEZ-FANDOS; ELISABET FERRER; RAQUEL PUIG-PEIX; CRISTINA CARREÑO; NEUS PRAT; MÓNICA APARICI; MELINA MARA MUSRI; AMADEU GAVALDA; VICTOR IVO PEINADO; MONTSERRAT MIRALPEIX; JOAN ALBERT BARBERÀ
Revista:
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
Editorial:
AMER THORACIC SOC
Referencias:
Lugar: New York; Año: 2014 vol. 50 p. 337 - 346
ISSN:
1044-1549
Resumen:
Long-acting muscarinic antagonists are widely used to treat chronic
obstructive pulmonary disease (COPD). In addition to bronchodilation,
muscarinic antagonismmay affect pulmonary histopathological changes.
The effects of long-acting muscarinic antagonists have not been
thoroughly evaluated in experimental models of COPD induced by
chronic exposure to cigarette smoke (CS). We investigated the effects of
aclidinium bromide on pulmonary function, airway remodeling, and
lung inflammation in aCS-exposedmodel of COPD.Atotal of 36 guinea
pigs were exposed toCS and 22 weresham exposed for 24 weeks. Animals
were nebulized daily with vehicle, 10 mg/ml, or 30 mg/ml aclidinium,
resulting in six experimental groups. Pulmonary function was assessed
weekly by whole-body plethysmography, determining the enhanced
pause (Penh) at baseline, after treatment, and after CS/sham
exposure. Lung changes were evaluated by morphometry and
immunohistochemistry. CS exposure increased Penh in all conditions.
CS-exposed animals treatedwith aclidinium showed lower baseline Penh
than untreated animals (P = 0.02).CS induced thickening of all bronchial
wall layers, airspace enlargement, and inflammatory cell infiltrate in
airways and septa. Treatment with aclidinium abrogated the CS-induced
smooth muscle enlargement in small airways (P = 0.001), and tended
to reduce airspace enlargement (P = 0.054). Aclidinium also attenuated
CS-induced neutrophilia in alveolar septa (P = 0.04). We conclude that,
in guinea pigs chronically exposed to CS, aclidinium has an antiremodeling effect on small airways, which is associated with
improved respiratory function, and attenuates neutrophilic infiltration in
alveolar septa. These results indicate that, inCOPD, aclidiniummayexert
beneficial effects on lung structure in addition to its bronchodilator
action.