Exploring the role of CT densitometry: a randomised study of augmentation therapy in α1-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 α1-antitrypsin (α1-AT) deficiency.In total, 77 subjects (protease inhibitor type Z) were randomised to weekly infusions of 60 mg·kg−1human α1-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®versusplacebo ranged 0.049–0.084). Exacerbation frequency was unaltered by treatment, but a reduction in exacerbation severity was observed.In patients with α1-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 α1-AT augmentation.