Exploring the role of CT densitometry: a randomised study of augmentation therapy in alpha1-antitrypsin deficiency

A Dirksen; E Piitulainen; D G Parr; C Deng; M Wencker; S B Shaker; R A Stockley

doi:10.1183/09031936.00159408

Exploring the role of CT densitometry: a randomised study of augmentation therapy in alpha1-antitrypsin deficiency

A Dirksen, E Piitulainen, D G Parr, C Deng, M Wencker, S B Shaker, R A Stockley

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

305 Citationer (Scopus)

Abstract

Udgivelsesdato: 2009-Jun

Originalsprog	Engelsk
Tidsskrift	European Respiratory Journal
Vol/bind	33
Udgave nummer	6
Sider (fra-til)	1345-53
Antal sider	9
ISSN	0903-1936
DOI	https://doi.org/10.1183/09031936.00159408
Status	Udgivet - 2009

Bibliografisk note

Keywords: Densitometry; Disease Progression; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Placebos; Pulmonary Emphysema; Regression Analysis; Reproducibility of Results; Tomography, X-Ray Computed; Treatment Outcome; Trypsin Inhibitors; alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency

Adgang til dokumentet

10.1183/09031936.00159408

Citationsformater

@article{05a28cd0791411df928f000ea68e967b,

title = "Exploring the role of CT densitometry: a randomised study of augmentation therapy in alpha1-antitrypsin deficiency",

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 x kg(-1) human alpha(1)-AT (Prolastin) 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 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 = "A Dirksen and E Piitulainen and Parr, {D G} and C Deng and M Wencker and Shaker, {S B} and Stockley, {R A}",

note = "Keywords: Densitometry; Disease Progression; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Placebos; Pulmonary Emphysema; Regression Analysis; Reproducibility of Results; Tomography, X-Ray Computed; Treatment Outcome; Trypsin Inhibitors; alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency",

year = "2009",

doi = "10.1183/09031936.00159408",

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T1 - Exploring the role of CT densitometry: a randomised study of augmentation therapy in alpha1-antitrypsin deficiency

AU - Dirksen, A

AU - Piitulainen, E

AU - Parr, D G

AU - Deng, C

AU - Wencker, M

AU - Shaker, S B

AU - Stockley, R A

N1 - Keywords: Densitometry; Disease Progression; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Placebos; Pulmonary Emphysema; Regression Analysis; Reproducibility of Results; Tomography, X-Ray Computed; Treatment Outcome; Trypsin Inhibitors; alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency

PY - 2009

Y1 - 2009

N2 - 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 x kg(-1) human alpha(1)-AT (Prolastin) 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 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.

AB - 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 x kg(-1) human alpha(1)-AT (Prolastin) 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 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.

U2 - 10.1183/09031936.00159408

DO - 10.1183/09031936.00159408

M3 - Journal article

C2 - 19196813

SN - 0903-1936

VL - 33

SP - 1345

EP - 1353

JO - European Respiratory Journal

JF - European Respiratory Journal

IS - 6

ER -