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Exploring the role of CT densitometry: a randomised study of augmentation therapy in alpha(1)-antitrypsin deficiency

Dirksen, A.; Piitulainen, Eeva LU ; Parr, D. G.; Deng, C.; Wencker, M.; Shaker, S. B. and Stockley, R. A. (2009) In European Respiratory Journal1988-01-01+01:00 33(6). p.1345-1353
Abstract
Assessment of emphysema-modifying therapy is difficult, but newer outcome measures offer advantages over traditional methods. The EXAcerbations and Computed Tomography scan as Lung End-points (EXACTLE) trial explored the use of computed tomography (CT) densitometry and exacerbations for the assessment of the therapeutic effect of augmentation therapy in subjects with alpha(1)-antitrypsin (alpha(1)-AT) deficiency. In total, 77 subjects (protease inhibitor type Z) were randomised to weekly infusions of 60 mg.kg(-1) human alpha(1)-AT (Prolastin (R)) or placebo for 2-2.5 yrs. The primary end-point was change in CT lung density, and an exploratory approach was adopted to identify optimal methodology, including two methods of adjustment for lung... (More)
Assessment of emphysema-modifying therapy is difficult, but newer outcome measures offer advantages over traditional methods. The EXAcerbations and Computed Tomography scan as Lung End-points (EXACTLE) trial explored the use of computed tomography (CT) densitometry and exacerbations for the assessment of the therapeutic effect of augmentation therapy in subjects with alpha(1)-antitrypsin (alpha(1)-AT) deficiency. In total, 77 subjects (protease inhibitor type Z) were randomised to weekly infusions of 60 mg.kg(-1) human alpha(1)-AT (Prolastin (R)) or placebo for 2-2.5 yrs. The primary end-point was change in CT lung density, and an exploratory approach was adopted to identify optimal methodology, including two methods of adjustment for lung volume variability and two statistical approaches. Other end-points were exacerbations, health status and physiological indices. CT was more sensitive than other measures of emphysema progression, and the changes in CT and forced expiratory volume in 1 s were correlated. All methods of densitometric analysis concordantly showed a trend suggestive of treatment benefit (p-values for Prolastin (R) versus placebo ranged 0.049-0.084). Exacerbation frequency was unaltered by treatment, but a reduction in exacerbation severity was observed. In patients with alpha(1)-AT deficiency, CT is a more sensitive outcome measure of emphysema-modifying therapy than physiology and health status, and demonstrates a trend of treatment benefit from alpha(1)-AT augmentation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
alpha(1)-Antitrypsin deficiency, computed tomography, emphysema, exacerbations, lung densitometry, lung function
in
European Respiratory Journal1988-01-01+01:00
volume
33
issue
6
pages
1345 - 1353
publisher
Eur Respiratory Soc
external identifiers
  • wos:000267301800016
  • scopus:67649407825
ISSN
1399-3003
DOI
10.1183/09031936.00159408
language
English
LU publication?
yes
id
008d444f-a7b3-4bfc-826e-db36d400fd36 (old id 1441427)
date added to LUP
2009-07-28 09:17:02
date last changed
2017-11-12 03:23:34
@article{008d444f-a7b3-4bfc-826e-db36d400fd36,
  abstract     = {Assessment of emphysema-modifying therapy is difficult, but newer outcome measures offer advantages over traditional methods. The EXAcerbations and Computed Tomography scan as Lung End-points (EXACTLE) trial explored the use of computed tomography (CT) densitometry and exacerbations for the assessment of the therapeutic effect of augmentation therapy in subjects with alpha(1)-antitrypsin (alpha(1)-AT) deficiency. In total, 77 subjects (protease inhibitor type Z) were randomised to weekly infusions of 60 mg.kg(-1) human alpha(1)-AT (Prolastin (R)) or placebo for 2-2.5 yrs. The primary end-point was change in CT lung density, and an exploratory approach was adopted to identify optimal methodology, including two methods of adjustment for lung volume variability and two statistical approaches. Other end-points were exacerbations, health status and physiological indices. CT was more sensitive than other measures of emphysema progression, and the changes in CT and forced expiratory volume in 1 s were correlated. All methods of densitometric analysis concordantly showed a trend suggestive of treatment benefit (p-values for Prolastin (R) versus placebo ranged 0.049-0.084). Exacerbation frequency was unaltered by treatment, but a reduction in exacerbation severity was observed. In patients with alpha(1)-AT deficiency, CT is a more sensitive outcome measure of emphysema-modifying therapy than physiology and health status, and demonstrates a trend of treatment benefit from alpha(1)-AT augmentation.},
  author       = {Dirksen, A. and Piitulainen, Eeva and Parr, D. G. and Deng, C. and Wencker, M. and Shaker, S. B. and Stockley, R. A.},
  issn         = {1399-3003},
  keyword      = {alpha(1)-Antitrypsin deficiency,computed tomography,emphysema,exacerbations,lung densitometry,lung function},
  language     = {eng},
  number       = {6},
  pages        = {1345--1353},
  publisher    = {Eur Respiratory Soc},
  series       = {European Respiratory Journal1988-01-01+01:00},
  title        = {Exploring the role of CT densitometry: a randomised study of augmentation therapy in alpha(1)-antitrypsin deficiency},
  url          = {http://dx.doi.org/10.1183/09031936.00159408},
  volume       = {33},
  year         = {2009},
}