Automated selective extraction of the lungs, trachea, and main bronchi from the CT scan volume was performed. High-density intraparenchymal structures excluded by the dynamic threshold-based lung extraction technique (including intraparenchymal blood vessels, fissures) were reincorporated in the calculations of final lung volumes based on the technique of “hole closing” to more accurately represent true lung volumes than simple threshold-based extraction techniques (Fig 1). Median 3-D filtration of the CT scan datasets was performed with a 3 X 3 X 3 neighborhood as a processing step prior to emphysema quantification. The median filter was used to remove noise and other spurious features of single pixel extent while preserving overall image quality, to reduce the contribution of image noise to the emphysema counts and increase the accuracy of emphysema volume in these low-dose CT scans with overlapping slices.

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Quantitative measures of lung density were performed and a threshold of -900 Hounsfield units (HU) was chosen to estimate emphysema volume in the extracted lung volume. The volume of low attenuation voxels was then divided by the total lung volume to obtain the percentage of emphysema.

Spirometry

Spirometry was performed using a Puritan Bennett Renaissance pneumotach-based flow spirometer (Mallinckrodt; St Louis, MO) according to the standards set by the American Thoracic Society/ European Respiratory Society. Flows were expressed as percentage of predicted using the reference equations of Crapo et al.

Canadian Pharmacy Statistical Analysis

All analyses were performed using the 1:6 matched set of 64 cases and 377 control subjects selected from participants of the lung cancer screening trial without evidence of cancer. There were seven cases that had only five matches. These additional control subjects were excluded from the study because their data sets could not be processed or because of significant artifacts (such as beam hardening from metal in the thorax, significant image noise from large patient size, patient motion, problems with the CT scan acquisition, protocol deviation, or loss of image data since the acquisition in 1999). Conditional logistic regression was used to assess whether percent predicted FEVj, FEV/FVC, or the percentage of emphysema were risk factors for lung cancer.