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dc.contributor.authorOrgan, Louise
dc.contributor.authorBacci, Barbara
dc.contributor.authorKoumoundouros, Emmanuel
dc.contributor.authorBarcham, Garry
dc.contributor.authorMilne, Marjorie
dc.contributor.authorKimpton, Wayne
dc.contributor.authorSamuel, Chrishan
dc.contributor.authorSnibson, Ken
dc.date.accessioned2015-09-01T18:29:11Z
dc.date.available2015-09-01T18:29:11Z
dc.date.issued2015-07-31
dc.identifier.citationBMC Pulmonary Medicine. 2015 Jul 31;15(1):81
dc.identifier.urihttp://dx.doi.org/10.1186/s12890-015-0071-6
dc.identifier.urihttp://hdl.handle.net/10724/32032
dc.description.abstractAbstract Background Idiopathic pulmonary fibrosis (IPF) is a severe and progressive respiratory disease with poor prognosis. Despite the positive outcomes from recent clinical trials, there is still no cure for this disease. Pre-clinical animal models are currently largely limited to small animals which have a number of shortcomings. We have previously shown that fibrosis is induced in isolated sheep lung segments 14 days after bleomycin treatment. This study aimed to determine whether bleomycin-induced fibrosis and associated functional changes persisted over a seven-week period. Methods Two separate lung segments in nine sheep received two challenges two weeks apart of either, 3U bleomycin (BLM), or saline (control). Lung function in these segments was assessed by a wedged-bronchoscope procedure after bleomycin treatment. Lung tissue, and an ex vivo CT analysis were used to assess for the persistence of inflammation, fibrosis and collagen content in this model. Results Fibrotic changes persisted up to seven weeks in bleomycin-treated isolated lung segments (Pathology scores: bleomycin12.27 ± 0.07 vs. saline 4.90 ± 1.18, n = 9, p = 0.0003). Localization of bleomycin-induced injury and increased tissue density was confirmed by CT analysis (mean densitometric CT value: bleomycin −698 ± 2.95 Hounsfield units vs. saline −898 ± 2.5 Hounsfield units, p = 0.02). Masson’s trichrome staining revealed increased connective tissue in bleomycin segments, compared to controls (% blue staining/total field area: 8.5 ± 0.8 vs. 2.1 ± 0.2 %, n = 9, p < 0.0001). bleomycin-treated segments were significantly less compliant from baseline at 7 weeks post treatment compared to control-treated segments (2.05 ± 0.88 vs. 4.97 ± 0.79 mL/cmH20, n = 9, p = 0.002). There was also a direct negative correlation between pathology scores and segmental compliance. Conclusions We show that there is a correlation between fibrosis and correspondingly poor lung function which persist for up to seven weeks after bleomycin treatment in this large animal model of pulmonary fibrosis.
dc.titleStructural and functional correlations in a large animal model of bleomycin-induced pulmonary fibrosis
dc.typeJournal Article
dc.date.updated2015-07-31T03:42:59Z
dc.language.rfc3066en
dc.rights.holderOrgan et al.


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