PT  - JOURNAL ARTICLE
AU  - Aran Singanayagam
AU  - Nicholas Glanville
AU  - Nathan Bartlett
AU  - Sebastian Johnston
TI  - LSC 2013 abstract - Development of a mouse model of COPD exacerbation
DP  - 2013 Sep 01
TA  - European Respiratory Journal
PG  - PP159
VI  - 42
IP  - Suppl 57
4099  - http://erj.ersjournals.com/content/42/Suppl_57/PP159.short
4100  - http://erj.ersjournals.com/content/42/Suppl_57/PP159.full
SO  - Eur Respir J2013 Sep 01; 42
AB  - Introduction: There are few existing mouse models of chronic obstructive pulmonary disease(COPD) exacerbation. Protocols include single or multiple doses of elastase(EL), different intervals between EL administration and infection and/or addition of lipopolysaccharide(LPS). Our aim was to develop a mouse model of rhinovirus(RV) induced COPD exacerbation that closely resembled human disease.Methods: 10 week C57BL/6 mice were exposed intranasally to 1,2,3 or 4 weeks of 1.2U EL +/- 7µg LPS, followed by infection with RV1B or UV inactivated RV,1 or 2 weeks after EL/LPS dosing.Results: Reduced virus loads and inflammation were seen in EL-LPS treated mice compared to PBS treated mice, regardless of whether 1,2,3 or 4 weeks of dosing was administered. Histological emphysema was present in EL-LPS mice, regardless of duration of exposure(data not shown). Single dose EL or EL-LPS protocols followed by 1 or 2 week interval to infection showed similar virus loads across RV-infected groups(fig1). However, there were significantly increased bronchoalveolar lavage neutrophils and Muc5AC gene expression at 1 day post infection in EL-LPS mice infected after a 2 week interval compared to PBS+RV mice(fig1).Conclusion: A protocol of single dose EL+LPS followed by 2 week interval to infection produces phenotypes that most closely resemble human exacerbation. This model may be useful for investigating disease mechanisms and in vivo testing of novel therapies.