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Principal Investigator
Paul Kvale
Henry Ford Health System
Position Title
About this CDAS Project
NLST (Learn more about this study)
Project ID
Initial CDAS Request Approval
Apr 12, 2005
Objective Measure of Lung Density in Emphysema Using CT
Previous investigations have suggested that computed tomography (CT) could be used to quantitate the degree of emphysema in patients with severe a1-antitrypsin deficiency (a1 -AT). Since 1984 computed tomography (CT) has been used to diagnose and quantify emphysema. A recent longitudinal study of emphysema in smokers with a1 -AT showed that CT densitometry of the lung was more sensitive in showing the progression of emphysema when compared with standard lung function tests. It has been purported that novel therapies have demonstrated slowing of the progression of the disease through measurements made from CT. Few longitudinal studies have been performed to follow the loss of lung density, and thus the progress of emphysema, in smokers without a1 -AT but with smoking-related emphysema. This study will review serial CT scans from subjects enrolled in the NLST to determine the natural history of loss of lung density. Objective quantification of emphysema is central to the understanding of the severity of disease, extent of disease, and to monitor the progression of disease. Using CT, the density of the lung can be measured. Each three dimensional voxel has its own density as measured by attenuation of the x-ray beam and is expressed in Hounsfield Units (HU). Density of lung tissue can be measured with reliable reproducibility and with considerable accuracy with the newer spiral CT technique. One method of analysis of lung density uses the density value in HU at which 15% of the lung voxels have a lower density. Using this methodology, it has been demonstrated that the annual decline of lung density of patients with a1 -AT is 2.5 +/- 0.4 HU per year measured on a spiral CT scanner. Based on these encouraging results from a previous longitudinal study, the HU value of th 15th percentile value will be chosen as the effect variable for the entire lung. We will also use a 3D analysis algorithm to calculate total lung volume, mean lung density, and percent lung volume with attenuation values less than an air threshold. The air threshold will be set for each measurement at a value equal to the mean air value in the trachea plus two standard deviations. These measurements will enable us to observe the natural history of loss of lung density over two years. We will compare the loss of lung density in smokers without visual emphysema on baseline CT scan to the loss of density in smokers with qualitative emphysema present on their baseline scan. In both groups, we will also review clinical records of the subjects to see if pulmonary function data is also available, but there will be no systematic attempt to correlate matching yearly CT density changes with pulmonary function test results. Our primary endpoint will be to quantitate the natural history of change in lung density over time in subjects with smoking-related emphysema

Pulmonary emphysema is a disorder characterized by the destruction of alveolar walls with loss of elastic recoil and subsequent hyperinflation. It subsequently affects parenchymal tissue mass and air volumes. In the early stages of disease, emphysema is characterized by lung distention with little changes in overall lung volume. Only with progression of the disease does lung volume and lung density change. Computed tomography scans of the lung reveal changes in lung volume in moderate to severe emphysema. Classification of the extent and severity of emphysema is usually limited by the experience of the radiologist reading the scan, who determines the severity of emphysema based on a visual emphysema score. This method is fraught with limitations, with the most pronounced being the lack of reproducibility between readers and between individual scans. Both the involvement of specific lung regions as well as overall degree of pulmonary emphysema can be quantified based on calculations of lung volume and density in regions of interest. This method is advantageous in that reader dependence is eliminated; both accuracy and precision of the scans yield reproducibility across readers of varying skill levels as well as among scans performed at differing institutions. This technology may have an important and ever increasing role in the diagnosis and quantification of pulmonary emphysema. While there have been studies evaluating the distribution of lung density or structure in pulmonary emphysema, few longitudinal studies exist to measure changes in lung volume and density over time. Fewer still attempt to correlate this with changes in lung function. This study aims to evaluate the natural history of lung density changes on CT in emphysema by 1) determining total lung volume and mean lung density; 2) quantifying the percentage of total lung volume that is affected by emphysema ; 3) determining the mean density of the volume represented by emphysema; 4) determining the 15 percentile point, a sensitive marker of early emphysema; and to 5) monitor the natural history of emphysema in two years by determining the changes in these parameters over each yearly measurement, and comparing smokers without qualitative emphysema on their baseline CT to smokers with qualitative emphysema. PFT Proposal Addendum As stated in the original protocol, Objective Measure of Lung Density in Emphysema Using CT we reviewed medical records of our subjects for PFT data. Less than 10 percent of subjects had PFT data available in their medical records. Our group decided that having a larger sample of subjects with and without qualitative emphysema with PFT data would strengthen the data and allow us to determine the extent of clinical disease in our subjects. Thus we are submitting this modification toour earlier proposal.