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|Title: ||Non-invasive assessment of ventilation maldistribution in lung disease using multiple breath inert gas washouts.|
|Authors: ||Horsley, Alex|
|Supervisor(s): ||Innes, Alastair|
Greening, Andrew P.
|Issue Date: ||2009|
|Publisher: ||The University of Edinburgh|
|Abstract: ||Clinical research in cystic fibrosis (CF) requires study endpoints that are
sensitive to airways disease, repeatable and non-invasive. Despite significant
advances in the treatment of CF, lung function assessments continue to rely on the
forced expiratory volume in 1 second (FEV1). Although simple to perform, it lacks
sensitivity, is difficult for younger subjects, and changes over time. An alternative
method of assessing lung physiology is to derive measures of ventilation
heterogeneity from inert gas washout tests. In early lung disease, measures of gas
mixing appear to be more sensitive than spirometry. In addition, since only tidal
breathing is required, they are more physiological and are more straightforward for
younger subjects. Widespread use has been impaired by the lack of a robust and cost
effective gas analyser technology.
The work presented in this thesis concerns the adaptation, validation and then
use of a novel gas analyser (Innocor) in a clinical system for the performance of
multiple breath washouts. Lung clearance index (LCI), a simple measure of
ventilation heterogeneity, has been calculated from washouts in 52 adults with CF
and 50 healthy controls. LCI was more sensitive to disease than FEV1 in CF, being
elevated in 11 of the 12 CF patients with normal spirometry. In healthy subjects, LCI
has been shown to be repeatable and reproducible, with a narrow range of normal
that is stable over a wide age range.
In a separate study of 19 patients, LCI has also been shown to improve with
treatment of an exacerbation in CF. Correlation with changes in other biochemical
(serum CRP, peripheral blood white cell count, sputum IL-8, sputum neutrophil)
clinical (symptom score) or structural (computed tomography) markers was poor.
Short term change in LCI has also been demonstrated in CF patients in response to
chest physiotherapy, although there was considerable heterogeneity of response in
terms of both LCI and volume of lung ventilated by tidal breathing (as measured by
washout functional residual capacity).
In addition to LCI, multiple breath phase III slope analysis has been performed
on washouts of CF patients and healthy controls, and this has been compared to other
measures of lung physiology. Proposed measures of convective and diffusive gas
mixing have been shown to be unreliable in CF. These studies have also been the
first to demonstrate multi-centre use of washout tests as endpoints.
The technology described here offers the possibility of a simple and reliable
system for performing multiple breath washouts, though at present it is not available
commercially. The studies have added to the understanding of the utility and
reliability of washout tests, as well as some of their limitations. It is hoped that in
future LCI will be an important clinical endpoint in therapeutic intervention studies
in CF, and that it will also offer new ways to follow changes in lung physiology in
|Sponsor(s): ||wholly funded by the UK Cystic Fibrosis Gene Therapy Consortium|
|Keywords: ||lung clearance index|
multiple breath washout
|Appears in Collections:||School of Clinical Sciences thesis and dissertation collection|
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