University of Oulu

Histopathological features in the progression of idiopathic pulmonary fibrosis/usual interstitial pneumonia with special emphasis on the redox modulating enzymes of the human lung

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Author: Tiitto, Leena1,2,3,4,5
Organizations: 1University of Oulu, Faculty of Medicine, Department of Internal Medicine
2University of Oulu, Faculty of Medicine, Department of Pathology
3Oulu University Hospital
4University of Helsinki, Faculty of Medicine
5University of Helsinki, Faculty of Medicine, Division of Pulmonary Diseases
Format: ebook
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.9 MB)
Persistent link: http://urn.fi/urn:isbn:9514282078
Language: English
Published: 2006
Publish Date: 2006-09-13
Thesis type: Doctoral Dissertation
Defence Note: Academic dissertation to be presented, with the assent of the Faculty of Medicine of the University of Oulu, for public defence in Auditorium 10 of Oulu University Hospital, on September 22nd, 2006, at 12 noon
Reviewer: Docent Sisko Anttila
Docent Lauri Tammilehto
Description:

Abstract

Interstitial lung diseases (ILD), including interstitial pneumonias (IP), represent disorders with variable degrees of parenchymal inflammation and/or fibrosis offer an ideal model to investigate the histopathological features in relation to the course of these diseases. The most common IP is idiopathic pulmonary fibrosis (IPF) with the histological pattern of usual interstitial pneumonia (UIP) exhibiting the histological hallmark of fibroblast foci (FF). Surgical lung biopsy (SLB) is not usually needed for diagnosis of IPF, but the lung biopsy samples taken by SLB confers the diagnosis in atypical cases. The safety of SLB in IPF/UIP has been a controversial issue. The acute exacerbation occasionally occurs during the course of IPF/UIP, but pathological features related to this event are poorly understood.

Recent studies suggest that one important determinant in the pathogenesis of ILDs, as in IPF, is oxidant stress and an imbalance of the redox-state in the lung. Thiol containing redox-regulated proteins which paticipate in the antioxidant defence of the lung include thiorexin (Trx) and gamma-glutamylcysteine synthetase (γGCS), also called glutamate-cysteine ligase (GLCL), the rate-limiting enzyme of glutathione (GSH) synthesis.

The goal of this research was to evaluate the safety of SLB and the relationships between the histological findings and the course of IPF/UIP, and to investigate the above mentioned defense mechanisms in a variety of ILDs by means of immmunohistochemical analyses, Western Blotting and immunoelectronmicroscopy.

No deaths occurred in the following 30 days after 34 video-assisted thoracoscopic lung biopsy (VATS). The number of FF in the lung sample predicted the survival, but it was not associated with acute exacerbation of IPF/UIP before death. Diffuse alveolar damage was a common feature in autopsy samples. The studied redox regulated defense enzymes were expressed in bronchial epithelium, metaplastic alveolar epithelium and alveolar macrophages, but the fibrotic areas generally showed no expression.

In IPF/UIP VATS is a safe diagnostic method and counting the number of FF represents a reproducible and reliable method for predicting patient survival. Alterations in the redox regulated defense enzymes further point to the importance of oxidant burden in the fibrotic lung.

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Series: Acta Universitatis Ouluensis. D, Medica
ISSN-E: 1796-2234
ISBN: 951-42-8207-8
ISBN Print: 951-42-8206-X
Issue: 891
Subjects:
Copyright information: © University of Oulu, 2006. This publication is copyrighted. You may download, display and print it for your own personal use. Commercial use is prohibited.