This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypotheses are: AATD subjects with normal lung function-FEV1 greater or equal to 80 percent predicted, and abnormal QCT have a greater rate of decline in FEV1- ml/year than AATD subjects with a normal QCT; loss of lung parenchyma determined by QCT significantly correlates with lung function decline and COPD progression; lung inflammation as measured by CRP correlates with loss of lung function and lung parenchyma determined by QCT. Secondary analyses will evaluate the correlation of QTC with other measures of lung function, and inflammatory biomarkers. Participation of these subjects in the Alpha-1 Foundation DNA and Tissue Bank will be encouraged to link the CT outcomes of this study to single nucleotide polymorphisms of candidate COPD susceptibility genes that are being evaluated in current AATD studies. To address these hypotheses, we will conduct a 3-year longitudinal study in 50 individuals with AATD with normal lung function. The baseline QCT will define the percentage of lung less than-910 Hounsfield units and the median value will be chosen to divide the subjects into those with greater lung density and those with less lung density. We will monitor inspiratory QCTs at a high and low resolution at every visit and expiratory QCTs at visit 1 and at the end of year 2. Secondary and exploratory analyses will assess the optimal radiographic technique for correlation with FEV1 decline. This study will pilot the development of a more accurate assessment of lung tissue loss and may improve the understanding of the lung destruction in AATD individuals.
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