Background and purpose: Acute exacerbations of chronic obstructive pulmonary disease (COPD), which are often associated with respiratory infections, are defined as a worsening of symptoms that require a change in medication. Exacerbations are characterized by a reduction in lung function, quality of life and are associated with increased pro-inflammatory mediators in the lung. Our aim was to develop an animal model to mimic aspects of this exaggerated inflammatory response by combining key etiological factors, tobacco smoke (TS) and bacterial lipopolysaccharide (LPS).
Experimental approach: Rats were exposed to TS for 30 min twice a day for 2 days. On day 3 animals were exposed to LPS for 30 min followed by exposure to TS 5 h later. Inflammation, mucus and lung function were assessed 24 h after LPS.
Key results: Neutrophils, mucus, oedema and cytotoxicity in lung and/or bronchoalveolar lavage was increased in animals exposed to combined LPS and TS, compared with either stimulus alone. Lung function was impaired in animals exposed to combined LPS and TS. Inflammatory cells, oedema and mucus were unaffected by pretreatment with the corticosteroid, budesonide, but were reduced by the phosphodiesterase 4 selective inhibitor roflumilast. Additionally, lung function was improved by roflumilast.
Conclusions and implications: We have established an in vivo model mimicking characteristic features of acute exacerbations of COPD including lung function decline and increased lung inflammation. This model may be useful to investigate molecular and cellular mechanisms underlying such exacerbations, to identify new targets and to discover novel therapeutic agents.