Effects of Aclidinium Bromide in a Cigarette Smoke?Exposed Guinea Pig Model of Chronic Obstructive Pulmonary Disease

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

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY

AMER THORACIC SOC

Lugar: New York; Año: 2014 vol. 50 p. 337 - 346

1044-1549

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.