Mikolasch, Theresia Auguste;
(2023)
Transbronchial cryobiopsy and Neutrophil Lymphocyte Ratio - new precision medicine tools and markers in Interstitial Lung Disease.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The interstitial lung diseases (ILDs) are a group of over 200 disease that may lead to progressive fibrosis and respiratory failure. ILDs are heterogenous, with varying amounts of inflammation and fibrosis, and differ in response to therapy and outcome. The most severe fibrotic (f) ILD, idiopathic pulmonary fibrosis (IPF), has a median survival of just three years. Progressive fILD may respond to antifibrotic treatments which slow down, but do not reverse, fibrosis albeit often with significant side effects. Better treatments or delivery of treatments are needed. Diagnosis of ILD relies on clinical history, imaging and, in some cases lung biopsy, with associated risks. Better diagnostic and prognostic biomarkers in ILD are urgently needed. This thesis examines the approach to diagnosis, prognostication, and treatment in fILDs, and, in particular IPF. It begins with the finding that Neutrophil Lymphocyte Ratio (NLR), derived from a simple, widely available blood test, is a prognostic biomarker in IPF. The role of lung biopsy in the diagnostic pathway is considered and the use of a relatively new minimally invasive technique of transbronchial cryo lung biopsy (TBCB) as an alternative to surgical lung biopsy (SLB) is described. The value of TBCB to obtain lung tissue for research is demonstrated with evaluation of the distribution of inhaled ipratropium in fILD. Using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) on samples of lung taken using TBCB, it was demonstrated that inhaled medication was able to reach the fibrotic lung, presenting a new approach to drug delivery in fILD. Further discussion focusses on the current role of SLB in the diagnostic pathway in ILD, the presentation of a systematic literature review, and a discussion of future trials to assess the potential benefits of a wider use of TBCB.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Transbronchial cryobiopsy and Neutrophil Lymphocyte Ratio - new precision medicine tools and markers in Interstitial Lung Disease |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10175608 |
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