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Twenty-seven patients with diffuse fibrosing alveolitis (DFA), 27 patients with granulomatous lung disease (GLD), 3 patients with homozygous alpha 1-proteinase inhibitor deficiency (alpha 1-PID), and 6 healthy volunteers (C) were studied using thin section high resolution CT (HRCT) at 50% of actual vital capacity (VC), determined and controlled spirometrically during each exposure. A fast contour tracing algorithm was used to isolate the lung parenchyma followed by a quantitative histogram analysis of the frequencies of CT values. Mean CT values enabled us to discriminate significantly between the groups of C and alpha 1-PID. Significant differences were found between the groups of GLD and DFA versus C by applying suitably selected intervals of CT values. Moreover, if the patients were assigned to four different groups according to their lung function results (normal, restrictive, obstructive, restrictive and obstructive), again significant differences existed with respect to defined intervals of CT values. Mean CT values showed a significant negative correlation with lung function tests representative of lung parenchymal disease, i.e., VC, diffusing capacity, and exercise PaO2. Moreover, CT values ranging from -899 to -800 HU correlated positively, whereas CT value frequencies above -699 HU correlated inversely with these same lung function parameters. These results indicated that certain intervals of CT values do reflect functionally different abnormalities of lung parenchyma. It is concluded that an analysis of frequencies of CT values determined by spirometrically standardized HRCT provides objective quantitative data that reflect changes of pulmonary structure corresponding to lung function impairments. Thus, spirometrically standardized HRCT may be helpful for evaluating and staging patients with diffuse pulmonary disease.