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 60 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.

This study demonstrates that combination therapy with salmeterol/fluticasone compared with salmeterol monotherapy significantly reduces the frequency of moderate/severe exacerbations in patients with severe COPD.

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for the "Wissenschaftliche Arbeitsgemeinschaft zur Therapie von Lungenerkrankungen (WATL) α 1 -AT study group" Does α 1 -antitrypsin augmentation therapy slow the annual decline in FEV1 in patients with severe hereditary α 1 -antitrypsin deficiency? N. Seersholm, M. Wencker, N. Banik, K. Viskum, A. Dirksen, A. Kok-Jensen, N. Konietzko The ∆FEV1 in the treated group was significantly lower than in the untreated group, with annual declines of 53 mL·yr -1 (95% confidence interval (95% CI) 48-58 mL·yr -1 ) and 75 mL·yr -1 (95% CI 63-87 mL·yr -1 ), respectively (p=0.02). The two groups differed with respect to gender and initial FEV1% predicted. Gender did not have any influence on the ∆FEV1. Stratification by initial FEV1% pred showed a significant effect of the treatment only in the group of patients with an initial FEV1% pred of 31-65%, and ∆FEV1 was reduced by 21 mL·yr -1 .This nonrandomized study suggests that weekly infusion of human α 1 -antitrypsin in patients with moderately reduced lung function may slow the annual decline in forced expiratory volume in one second.