TY - JOUR T1 - Late intervention with a myeloperoxidase inhibitor prevents emphysema and small airway remodeling in the guinea pig JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p799 AU - Andrew Churg AU - Caroline Marshall AU - Don Sin AU - Elaine Cadogan AU - Matt Soars AU - Sarah Bolton AU - Justine Maltby AU - Philip Mallinder AU - Joanne Wright Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p799.abstract N2 - Considerable evidence links both inflammation and oxidative stress to the pathogenesis of COPD. Myeloperoxidase (MPO), a neutrophil product, plays a major role in bacterial killing via production of the powerful oxidant, HOCl. However, oxidants generated by MPO can damage tissue and MPO exerts a variety of other effects that drive inflammation. We examined the effects of an MPO inhibitor, AZ11938920 on chronic (6 month) cigarette smoke-induced lesions in the guinea pig. One group of animals received compound from smoking day 1 (prophylactic arm), whereas another group was only treated after 3 months of smoke exposure (therapeutic arm). Analysis of lavage fluid showed that both treatments abolished smoke-induced increases in lavage inflammatory cells. Both treatments prevented smoke-induced increases in airspace size (emphysema) and small airway remodeling. Physiologically, both treatments largely reversed smoke-induced shifts of the pressure-volume and flow-volume curves and returned resistance to control values. Both treatments prevented muscularization of the small intrapulmonary arteries, but only partially ameliorated smoke-induced pulmonary hypertension. Immunohistochemical staining for the oxidation product, dityrosine, was increased in smoke-exposed animals and this effect was largely reversed by both treatments. We conclude that a myeloperoxidase inhibitor is able to prevent the development of emphysema and small airway remodeling and to partially protect against pulmonary hypertension, even when treatment starts after 3 months of smoke exposure. This protection appears to be related to prevention of oxidant damage and suppression of inflammation. ER -