Validation of computed tomographic lung densitometry for monitoring emphysema in α1-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 alpha(1)-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: r(S) = 0.527, p = 0.001; voxel index: r(S) = 20.398, 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.