Tiotropium inhibits pulmonary inflammation and remodelling in a guinea pig model of COPD

• Published in: The European respiratory journal Vol. 38; no. 4; pp. 789 - 796
• Main Authors: PERA, T, ZUIDHOF, A, VALADAS, J, SMIT, M, SCHOEMAKER, R. G, GOSENS, R, MAARSINGH, H, ZAAGSMA, J, MEURS, H
• Format: Journal Article
• Language: English
• Published: Leeds Maney 01.10.2011
• Subjects: Acetylcholine - physiology; Airway Remodeling - drug effects; Airway Remodeling - immunology; Animals; Animals, Outbred Strains; Biological and medical sciences; Cholinergic Antagonists - pharmacology; Chronic obstructive pulmonary disease, asthma; Disease Models, Animal; Emphysema - drug therapy; Emphysema - immunology; Goblet Cells - drug effects; Goblet Cells - immunology; Goblet Cells - metabolism; Guinea Pigs; Lipopolysaccharides - toxicity; Lung - drug effects; Lung - immunology; Male; Medical sciences; Mucin 5AC - metabolism; Muscarinic Antagonists - pharmacology; Neutrophils - drug effects; Neutrophils - immunology; Pneumology; Pneumonia - drug therapy; Pneumonia - immunology; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - immunology; Pulmonary Fibrosis - drug therapy; Pulmonary Fibrosis - immunology; Scopolamine Derivatives - pharmacology; Tiotropium Bromide; Lung disease; Animal model; Respiratory disease; Tiotropium bromide; Lung; Rodentia; Airway remodelling; Inflammation; Vertebrata; Chronic; non-neuronal acetylcholine; Mammalia; Guinea pig; Animal; Blood vessel; Fibrosis; Lipopolysaccharide; Bronchus disease; Acetylcholine; Chronic obstructive pulmonary disease; pulmonary vascular remodelling; Obstructive pulmonary disease; Emphysema; Pneumology
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/09031936.00146610

Airway remodelling and emphysema are major structural abnormalities in chronic obstructive pulmonary disease (COPD). In addition, pulmonary vascular remodelling may occur and contribute to pulmonary hypertension, a comorbidity of COPD. Increased cholinergic activity in COPD contributes to airflow limitation and, possibly, to inflammation and airway remodelling. This study aimed to investigate the role of acetylcholine in pulmonary inflammation and remodelling using an animal model of COPD. To this aim, guinea pigs were instilled intranasally with lipopolysaccharide (LPS) twice weekly for 12 weeks and were treated, by inhalation, with the long-acting muscarinic receptor antagonist tiotropium. Repeated LPS exposure induced airway and parenchymal neutrophilia, and increased goblet cell numbers, lung hydroxyproline content, airway wall collagen and airspace size. Furthermore, LPS increased the number of muscularised microvessels in the adventitia of cartilaginous airways. Tiotropium abrogated the LPS-induced increase in neutrophils, goblet cells, collagen deposition and muscularised microvessels, but had no effect on emphysema. In conclusion, tiotropium inhibits remodelling of the airways as well as pulmonary inflammation in a guinea pig model of COPD, suggesting that endogenous acetylcholine plays a major role in the pathogenesis of this disease.