Exploring the optimum approach to the use of CT densitometry in a randomised placebo-controlled study of augmentation therapy in alpha 1-antitrypsin deficiency

• Published in: Respiratory research Vol. 10; no. 1; p. 75
• Main Authors: Parr, David G, Dirksen, Asger, Piitulainen, Eeva, Deng, Chunqin, Wencker, Marion, Stockley, Robert A
• Format: Journal Article
• Language: English
• Published: England BioMed Central 13.08.2009; BioMed Central Ltd; BMC
• Subjects: Absorptiometry, Photon - methods; alpha 1-Antitrypsin - administration & dosage; alpha 1-Antitrypsin Deficiency - complications; alpha 1-Antitrypsin Deficiency - diagnostic imaging; alpha 1-Antitrypsin Deficiency - drug therapy; Clinical Medicine; Clinical trials; Emphysema; Europe; Female; Frequency distribution; Humans; Klinisk medicin; Lungmedicin och allergi; Male; Medical and Health Sciences; Medical imaging; Medicin och hälsovetenskap; Middle Aged; Placebo Effect; Prognosis; Pulmonary Emphysema - diagnostic imaging; Pulmonary Emphysema - drug therapy; Pulmonary Emphysema - etiology; Quality Assurance, Health Care; Reproducibility of Results; Respiratory Medicine and Allergy; Sensitivity and Specificity; Tomography, X-Ray Computed - methods; Treatment Outcome; Trypsin Inhibitors - administration & dosage; Writing; United Kingdom > UK
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/1465-9921-10-75

Computed tomography (CT) lung densitometry has been demonstrated to be the most sensitive and specific outcome measure for the assessment of emphysema-modifying therapy, but the optimum densitometric index has yet to be determined and targeted sampling may be more sensitive than whole lung assessment. The EXAcerbations and CT scan as Lung Endpoints (EXACTLE) trial aimed to clarify the optimum approach to the use of CT densitometry data for the assessment of alpha 1-antitrypsin (AAT) augmentation therapy on the progression of emphysema in AAT deficiency (AATD). Patients with AATD (n = 77) were randomised to weekly infusions of 60 mg/kg human AAT (Prolastin) or placebo over 2 to 2.5 years. Lung volume was included as a covariate in an endpoint analysis and a comparison was made of different CT densitometric indices (15th percentile lung density [PD15], mean lung density [MLD] and voxel index at a threshold of -910 [VI-910] and -950 [VI-950] Hounsfield Units) obtained from whole lung scans at baseline and at 24 to 30 months. Targeted regional sampling was compared with whole lung assessment. Whole lung analysis of the total change (baseline to last CT scan) compared with placebo indicated a concordant trend that was suggestive of a treatment effect for all densitometric indices (MLD [1.402 g/L, p = 0.204]; VI-910 [-0.611, p = 0.389]; VI-950 [-0.432, p = 0.452]) and that was significant using PD15 (1.472 g/L, p = 0.049). Assessment of the progression of emphysema in the apical, middle and basal regions of the lung by measurement with PD15 showed that this treatment effect was more evident when the basal third was sampled (1.722 g/L, p = 0.040). A comparison between different densitometric indices indicated that the influence of inspiratory variability between scans was greatest for PD15, but when adjustment for lung volume was made this index was the most sensitive measure of emphysema progression. PD15 is the most sensitive index of emphysema progression and of treatment modification. Targeted sampling may be more sensitive than whole lung analysis. Registered in ClinicalTrials.gov as 'Antitrypsin (AAT) to Treat Emphysema in AAT-Deficient Patients'; ClinicalTrials.gov Identifier: NCT00263887.