CHRONIC OBSTRUCTIVE PULMONARY DISEASE Validation of computed tomographic lung densitometry for monitoring emphysema in a1-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 2950 Hounsfield units) to disease stage and FEV1 decline in two studies of subjects with a1-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 =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.