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Traditionally, determination of total lung capacity (TLC) by plethysmography (TLCpleth) has been important in the diagnosis of lung diseases. Alternatively, data acquired from computerized tomography (CT) can be utilized to calculate a measure of TLC (TLCCT). The clinical utility of TLCCT is not certain. We sought to determine, in a clinical setting, whether TLCCT correlates with TLCpleth across a range of lung diseases and scanning techniques. In addition, we determined whether TLCCT affects the interpretation of pulmonary function tests.Records of 118 of 148 consecutive lung transplant recipients were reviewed and determined to have coinciding pulmonary function tests, including plethysmography as well as volumetric chest CT performed supine during full inspiration. CT images acquired with a wide range of scanning protocols were analyzed using CALIPER, a software program for lung and trachea extraction from a CT volume and volumetric tissue characterization of the lung. Segmentation of the lung was achieved by using completely automated dynamic thresholding and region-growing techniques developed to extract the relatively low-density lung and tracheal anatomy from the CT data set without user intervention.TLCpleth and TLCCT were strongly related with a correlation coefficient of 0.88 (P<0.001). The efficacy of the CT-derived measure was not influenced by specific lung diagnoses, age, height, body mass index, or spirometric parameters. TLCCT did not misidentify any diagnosis of restrictive lung disease, nor hyperinflation.In a clinical setting, CT segmentation analysis provides a favorable determination of TLC compared with traditional plethysmography. The technique has general applicability across varying CT data acquisition protocols, lung diseases, and patient characteristics. TLCCT may substitute for TLCpleth in pulmonary function interpretation and may be preferable for some patients in whom plethysmography is difficult to perform, such as transplant subjects with severe pulmonary fibrosis.