title: Effects of aclidinium bromide in a cigarette smoke-exposed Guinea pig model of chronic obstructive pulmonary disease.
abstract: Long-acting muscarinic antagonists are widely used to treat chronic obstructive pulmonary disease (COPD). In addition to bronchodilation, muscarinic antagonism may 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 a CS-exposed model of COPD. A total of 36 guinea pigs were exposed to CS and 22 were sham exposed for 24 weeks. Animals were nebulized daily with vehicle, 10 μg/ml, or 30 μg/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 treated with 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, in COPD, aclidinium may exert beneficial effects on lung structure in addition to its bronchodilator action.
authors.affiliation: 1 Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Domínguez-Fandos
authors.forename: Elisabet
authors.initials: E
authors.lastname: Ferrer
authors.forename: Raquel
authors.initials: R
authors.lastname: Puig-Pey
authors.forename: Cristina
authors.initials: C
authors.lastname: Carreño
authors.forename: Neus
authors.initials: N
authors.lastname: Prats
authors.forename: Mònica
authors.initials: M
authors.lastname: Aparici
authors.forename: Melina Mara
authors.initials: MM
authors.lastname: Musri
authors.forename: Amadeu
authors.initials: A
authors.lastname: Gavaldà
authors.forename: Víctor I
authors.initials: VI
authors.lastname: Peinado
authors.forename: Montserrat
authors.initials: M
authors.lastname: Miralpeix
authors.forename: Joan A
authors.initials: JA
authors.lastname: Barberà
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004195:Disease Models, Animal; D006168:Guinea Pigs; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism; D012906:Smoke; D014026:Nicotiana; D014326:Tropanes / Q000494:pharmacology*
chemical_list: D018727:Muscarinic Antagonists; D012906:Smoke; D014326:Tropanes; C542859:aclidinium bromide