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

¹ Gentofte Hospital, Copenhagen University, Hellerup, Denmark
² University Hospital, Malmö, Sweden
³ University Hospitals of Coventry and Warwickshire, UK
⁴ Talecris Biotherapeutics Inc, Research Triangle Park, NC, USA
⁵ Talecris Biotherapeutics GmbH, Frankfurt, Germany
⁶ University Hospitals of Birmingham, UK

^* To whom correspondence should be addressed. E-mail: adi{at}dadlnet.dk.

	Abstract

Assessment of emphysema-modifying therapy is difficult, but newer outcome measures offer advantages over traditional methods. The EXAcerbations and CT scan as Lung Endpoints (EXACTLE) trial explored the use of CT densitometry and exacerbations for the assessment of the therapeutic effect of augmentation therapy in subjects with alpha-1 antitrypsin (AAT) deficiency.

Seventy-seven subjects (PiZ) were randomised to weekly infusions of 60 mg·kg^-1 human AAT (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 of CT and FEV₁ were correlated. All methods of densitometric analysis concordantly showed a trend suggestive of treatment benefit (p-values for Prolastin^® versus placebo ranged from 0.049–0.084). Exacerbation frequency was unaltered by treatment, but a reduction in exacerbation severity was observed.

In patients with AAT 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 AAT augmentation.

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