Validation of Computed Tomographic Lung Densitometry for Monitoring Emphysema in Alpha1-antitrypsin Deficiency

Background: Lung densitometry derived from computed tomographic images offers an opportunity to quantify emphysema non-invasively, but a pathological standard cannot be applied to validate its use in longitudinal monitoring studies. Consequently, forced expiratory volume in 1 second (FEV1) remains the standard against which new methods must be judged. We related progression of densitometry (15th percentile point and voxel index, threshold -950 Hounsfield units) to disease stage and FEV1 decline in two studies of subjects with alpha1-antitrypsin deficiency (PiZ).

Methods: Consistency of progression, measured using densitometry and FEV1, was assessed in relation to disease stage in a 2 year study of 74 subjects grouped according to the FEV1 criteria employed in the GOLD guidelines. In the second study of a subgroup of subjects with extended data (n=34), summary statistics were applied to measurements performed annually over 3 years and the rate of progression of densitometry was related to FEV1 decline.

Results: The progression of percentile point was consistent across a wide spectrum of disease severity, but voxel index progression varied in association with disease stage (p=0.004). In the second study, FEV1 decline correlated with progression of lung densitometry (percentile point: rS=0.527, p=0.001; voxel index: rS=-0.398, p=0.012).

Conclusions: 15th percentile point is a more consistent measure of lung density loss across a wide range of physiological impairment than voxel index. However, both methods are valid for use in longitudinal and interventional studies in which emphysema is the major outcome target.