|dc.contributor.author||Macleod, Kenneth Alexander||
|dc.description.abstract||Multiple breath washout (MBW) of inert gas for assessment of airway disease in
children is an emerging technique. In many studies Lung Clearance Index (LCI),
derived from multiple breath washout of SF6, is more able to detect early or mild
lung disease than standard lung function measurements. It is also able to detect very
early lung disease in progressive conditions such as Cystic Fibrosis (CF). Where
infants born with this condition were thought to have minimal lung disease activity,
LCI is higher in these children than healthy controls. Lack of available commercial
devices has hampered expansion of this technique to centres other than specialist
Innocor (Innovision, Dk), a photoacoustic mass spectrometer capable of performing
multiple breath washout, was adapted within this research group for use in adults.
This thesis describes the setup, adaptation and validation of Innocor for use in
In 4 studies, healthy controls, children with asthma and children with CF were
recruited to perform MBW.
In one study, 29 healthy controls and 31 children with asthma were recruited.
Healthy controls performed 1 set of washouts, establishing a normative range.
Children with asthma performed measurements before and after bronchodilator.
Results showed increased LCI in children with asthma even though they were
clinically stable as defined by symptoms. LCI stayed high even following
bronchodilator suggesting evidence of residual airway disease in well controlled
asthmatics despite adequate symptom control.
To investigate short term variability of MBW measurements, two other studies
recruited 18 children with CF in each. They performed measurements before and
after standard physiotherapy manoeuvres and during sitting and lying posture. LCI
did not change significantly after airway clearance physiotherapy, compared with
children who did no intervention. Variability was high in both groups however
suggesting CF lung disease is a complex interaction of changing ventilation in
adjacent lung units. Lying posture induced greater changes in lung function in
children with CF than controls. LCI appears to be more sensitive to this change than
standard lung function measurements (spirometry).
In another study 32 children with CF were recruited to perform serial lung function
measurements over 18 months. These were data collected as part of the UK Cystic
Fibrosis Gene Therapy Consortium (CFGTC) clinical studies in preparation for
planned gene therapy trials. LCI appears comparable to FEV1 and may be able to
detect another aspect of airway disease.
All initial studies were performed in older children (>5yrs). The basic Innocor device
is unsuitable for testing of younger patients with low breath volume and high
respiratory rate. In-house adaptations following detailed lung model experimentation
led to a faster analyser response, potentially capable of MBW in younger children.
The second part of this thesis concerns lab experiments and an in-vivo comparison
with the current gold-standard MBW device, a respiratory mass spectrometer. 16
healthy volunteers and 9 children with CF were recruited. Ages ranged from 0.4 yrs
to 49 yrs. Innocor values for lung volume estimation compared favourably with the
mass spectrometer. No evidence of bias caused by Innocor error was seen, however
intra-test variability was rather high, reducing the precision of the results.
These studies indicate Innocor is a robust, simple to use device with potential as a
commercial lung function system. Modifications were made to make it suitable for
use in all ages. Further development will need to focus on the patient interface and
software, which is the domain of the manufacturers. The experiments contained in
this thesis are therefore of interest to the wider respiratory research community as
well as manufacturers of MBW devices.||en
|dc.publisher||The University of Edinburgh||en
|dc.relation.hasversion||Ventilation heterogeneity in children with well controlled asthma with normal spirometry indicates residual airways disease. Macleod, K. A., Horsley, A. R., Bell, N. J., Greening, A. P., Innes, J. A. & Cunningham, S. (2009). Thorax, 64, 33-7||en
|dc.relation.hasversion||Effects of cystic fibrosis lung disease on gas mixing indices derived from alveolar slope analysis. Horsley, A. R., Macleod, K.A., Robson, A.G., Lenney, J., Bell, N.J., Cunningham, S., Greening, A.P., Gustafsson, P.M., Innes, J.A. Respir Physiol Neurobiol, 2008 Aug 31;162(3):197-203||en
|dc.relation.hasversion||Lung clearance index is a sensitive, repeatable and practical measure of airways disease in adults with cystic fibrosis. Horsley, A.R., Gustafsson, P.M., Macleod, K.A., Saunders, C., Greening, A.P., Porteous, D.J., Davies, J.C., Cunningham, S., Alton, E.W., Innes, J.A. Thorax. 2008 Feb;63(2):135-40.||en
|dc.relation.hasversion||Validation of the modified photo-acoustic gas analyser for in-vitro multiple breath washout in young children. Macleod, K.A., Irving, S., Bell, N., Horsley, A., Gustafsson, P., Bush, A., Cunningham, S. 2010. Eur Respir J, 703s||en
|dc.relation.hasversion||Lung clearance index, in children and adults with cystic fibrosis, is more sensitive to progressive airways disease than standard spirometry. Macleod, K. A., Horsley A. R., Bell, N. J., Reid, P., Davies, J., Alton, E. W., Greening, A. P., Innes, J. A., Cunningham, S. 2009 Am J Respir Crit Care Med 179, A5372||en
|dc.relation.hasversion||Modifications to a photoacoustic gas analyser increases accuracy of functional residual capacity measurements by multiple breath washout of SF6 in an infant lung model. Macleod, K., Horsley, A., Latzin, P., Bell, N., Innes, J.A., Cunningham, S. Eur Respir J 2008, 691s.||en
|dc.relation.hasversion||Acute changes in ventilation heterogeneity following routine physiotherapy in children with cystic fibrosis. Macleod, K., Dhouieb, E., Horsley, A., Bell, N., Greening, A., Innes, J.A., Cunningham, S. Eur Respir J 2008, 690s.||en
|dc.relation.hasversion||Evidence of persistent small airways disease measured by lung clearance index in well-controlled asthmatic children with normal FEV1. Macleod, K. A., Horsley, A. R., Bell, N. J., Greening, A. P., Innes, J. A. & Cunningham, S. 2007. Thorax 62 (Supplement 3): A39.||en
|dc.relation.hasversion||Development of standardisation criteria for the measurement of lung clearance index in a multi-centre study. Macleod, K., Horsley, A., Saunders, C., Innes, J.A., Alton, E., Davies, J., Cunningham, S. Eur Respir J 2007, 259s.||en
|dc.relation.hasversion||Lung clearance index is higher in asthmatic patients than healthy controls. Macleod, K., Horsley, A., Innes, J.A., Cunningham, S. 2007. Am J Respir Crit Care Med 175;||en
|dc.subject||paediatric lung function||en
|dc.subject||Multiple Breath Washout test||en
|dc.subject||photoacoustic mass spectrometer||en
|dc.title||Validation and application of a photo-acoustic gas analyser for multiple breath inert gas washout in children||en
|dc.type||Thesis or Dissertation||en
|dc.type.qualificationname||PhD Doctor of Philosophy||en