Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.506770
Title: A clinicopathological evaluation of abnormal lungepithelial markers in the interstitial lung disease of systemic sclerosis
Author: Goh, Nicole Soo Leng
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2008
Availability of Full Text:
Full text unavailable from EThOS.
Please contact the current institution’s library for further details.
Abstract:
Once thought to be an inflammatory-fibrotic disease, idiopathic pulmonary fibrosis (IPF) is regarded as an epithelial-fibrotic phenomenon with inflammation increasingly viewed as an epiphenomenon. Markers indicative of disruption in epithelial integrity have been associated with a worse outcome in IPF. However, these associations have only been minimally explored in the interstitial lung disease of systemic sclerosis (SScILD). This project tested the hypothesis that progression of SSc-ILD is linked to breaches of lung epithelial integrity. The aims were: 1) To study the prognostic significance of epithelial markers including 99mTc_DTPA pulmonary clearance and serum KL-6 levels and compare with other known prognostic markers. 2) To examine relationships between inhaled 99mTc_DTPA clearance and: a) histological features, b) bronchoalveolar lavage, in particular eosinophils, c) serum KL-6 levels. When traditional prognostic measures (HRCT, PFT, BAL) were assessed in SSc-ILD, baseline DLco levels, the extent of disease on HRCT and the extent of a reticular pattern on HRCT were all strong predictors of mortality. The extent of a reticular pattern on HRCT was the strongest predictor of disease progression. However, 99mTc_DTPA clearance was the strongest predictor of more progressive disease, surpassing the value of HRCT and PFT. Serum KL6 levels were predictive of more progressive disease but not of survival. BAL eosinophilia and/or neutrophilia have traditionally been viewed as markers of progression. Indeed, a BAL neutrophilia was found to be predictive of increased mortality in SSc-ILD but interestingly, this association was not significant after disease severity was controlled for. However, there was a significant correlation between 99mTc_ DTPA clearance and serum KL6 levels, and between 99mTc_DTPA clearance and BAL eosinophil levels. The profibrotic effects of eosinophils and their interactions with normal lung fibroblasts were further investigated by determining the contribution of profibrotic cytokines such as TGFp. Functional studies looking at the effects on pathologic indicators of fibrosis such as extraceullar matrix production and fibroblast proliferation were also performed Collectively, these results suggest that disruption to the epithelium may playa pivotal role in pathogenesis in SSc-ILD. Thus the use of 99mTc_DTPA pulmonary clearance may have a role in routine clinical practice. Perhaps of more practical use is the measurement of serum KL-6 levels, which is easily performed with no risk to the patient.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.506770  DOI: Not available
Share: