Date of Award

2010

Document type

Thesis

Degree Name

MD (Medical Doctor)

First Supervisor

Professor Gerry McElvaney

Keywords

Chronic Obstructive Pulmonary Disease

Abstract

Alpha-] Antitrypsin (AAT) deficiency is a genetically inherited disease characterized pathologically by panacinar emphysema, physiologically by obstructive spirometry. Individuals with AAT deficiency have symptoms of airways disease and some studies at post-mortem suggest that that individuals with AAT deficiency have pathological lesions similar to individuals with Chronic Obstructive Pulmonary Disease (COPD) such as goblet cell hyperplasia and increased epithelial wall thickness. Unlike COPD there are no quantitative studies of epithelial morphology in AAT deficiency. Therefore we sought to describe morphological changes in these both these diseases in a quantitative fashion using stereological techniques. We also assessed specific mucin protein expression using immunohistochemistry in both groups compared to normal never smoking subjects. In brief an endobronchial biopsy study was performed on 12 AAT deficient individuals, 11 COPD, and 5 non-smoking healthy control subjects. Biopsies were taken randomly throughout the R upper, lower and middle lobes. Biopsy samples were embedded in a glycolmythacralate resin for optimal morphologic assessment and sections were then stained for mucins using Alcian BlueIPAS. Using a design based stereological strategy epithelial height, epithelial mucin content, and cilia volume were measured. Individuals with AAT deficiency had airway epithelium that was morphologically similar to normal healthy controls. In contrast individuals with COPD had increased epithelial height, increased epithelial mucin content and reduced cilia by as much as 50% when compared to healthy controls with no lung disease. In addition the secreted mucins MUC 5AC, MUC 5B and MUC 19 were all expressed in the airways of AAT deficient individuals similar to normal healthy controls. MUC5AC was the principle mucin secreted in health and disease in the epithelium, there was also slight expression in the subrnucosal glands. MUCSB expression was predominantly in the submucosal glands but had increased expression in the epithelium of some individuals with COPD. Therewas no significant difference in the expression of MUC19 between all groups and expression appears to be primarily located in the submucosal glands.

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Comments

Submitted thesis for the degree of Doctor of Medicine, Royal College of Surgeons in Ireland, 2010