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Title: Histopathology of diffuse lung parenchyma epithelial metaplasia in COPD
Author: Brown, Kate Pinnion
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2010
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COPD is a chronic, multifactorial lung disease with multi-organ, systemic presentation that affects approximately 20% of smokers. Diffuse parenchymal epithelial metaplasia is seen in COPD patients and although rarely described, is usually considered to be Lambertosis, a reparative extension of airway epithelium. Cellular phenotype and pulmonary distribution of diffuse metaplasia was examined histologically and the cells characterised as either rounded and uniform, large and irregular resembling macrophages or squamous and flattened. The lesions were found to be localised to the external adventitia of the airways and vessels, sub pleural zone, hilar regions, ectopic fibrotic deposits and the external facet of alveolar epithelium. This distribution is not consistent with Lambertosis. This repair process hypothesis was evaluated by cellular markers consistent to known airway progenitors. No expression of CK5/6 basal nor CC10 Clara cell was detected. Surfactant presence suggested a type II phenotype indicating an alveolar origin. These findings further refute Lambertosis. The metaplastic population was further characterised using epithelial and progenitor markers. These cells displayed occasional multipotent, progenitor markers possibly originating from bone marrow or resident stem cells (CD34/CD133). The cytokeratin profile consistent with simple epithelium suggested new cell colonisation and mixed cytokeratin phenotype indicated a failure to mature. In addition to this evidence of repair response, metaplastic cells were found on expanded mesenchyme. This remodelled, scarred tissue further indicates damage and repair. Mutation detection of EGFR L858R by PCR did not show molecular changes indicative of early change in some adenocarcinoma, suggesting these cells do not progress to pre-neoplastic. From this, we can conclude that diffuse metaplasia in COPD peripheral lung is not consistent with Lambertosis. Overall, characteristics including surfactant and mucin presence, suggest a primitive epithelial phenotype, potentially a result of damage and aberrant repair.
Supervisor: Foster, Martyn ; Pringle, Howard Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available