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

A. Dirksen, E. Piitulainen, D. G. Parr, C. Deng, M. Wencker, S. B. Shaker, R. A. Stockley
2009 European Respiratory Journal  
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 a 1 -antitrypsin (a 1 -AT) deficiency. In total, 77 subjects (protease inhibitor type Z) were randomised to weekly infusions of
more » ... mg?kg -1 human a 1 -AT (Prolastin1) 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 Prolastin1 versus placebo ranged 0.049-0.084). Exacerbation frequency was unaltered by treatment, but a reduction in exacerbation severity was observed. In patients with a 1 -AT deficiency, CT is a more sensitive outcome measure of emphysemamodifying therapy than physiology and health status, and demonstrates a trend of treatment benefit from a 1 -AT augmentation.
doi:10.1183/09031936.00159408 pmid:19196813 fatcat:kixyijhitzeivcfr7xmcaiy54y