The potential usefulness of CT for identification of regions of pulmonary emphysema and air trapping has been addressed in many investigations [1]. Low-attenuation areas on CT scans in vivo have been found to represent macroscopic and microscopic emphysematous changes in the lungs of patients [2-4]. To objectively quantify pulmonary emphysema with CT, several lung attenuation parameters based on results of histogram analysis of the frequency distribution of the attenuation values of the lung have been developed. The most commonly used methods are based on measurement of mean lung attenuation, the areas of lung occupied by attenuation values lower than predetermined thresholds, and a predetermined percentile of the lung attenuation distribution curve. Many reports have confirmed good correlations of histogram-derived quantitative CT techniques with the results of lung function tests and pathologic evidence of emphysema [1].

The purpose of our study was to determine whether measurements of lung attenuation obtained from 3D lung reconstructions at inspiration and expiration reflect the severity of chronic obstructive pulmonary disease (COPD). We correlated lung function measurements at inspiration and expiration with measurements of lung attenuation on 3D lung reconstructions. We also evaluated the relation between the severity of COPD, reflected by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage [5], and measurements of lung attenuation on 3D lung reconstructions.

A total of 76 smokers were recruited at our institution. The 67 men and nine women (mean age, 67.3 years; range, 37-85 years) were included because they had a diagnosis of COPD according to the criteria of the American Thoracic Society [6]. All subjects were long-term cigarette smokers with an average smoking history of 1,142 ± 592 on the Brinkman index (cigarettes/day × years). According to the GOLD classification [5], six patients had stage 0; two, stage 1; 20, stage 2; 30, stage 3; and 18, stage 4 COPD (Table 1). The study was approved by the ethics committee of our hospital, and informed consent was obtained from each participant.

Table 2 shows the Spearman's correlation between CT parameters and results of pulmonary function tests. Histogram-derived quantitative CT techniques and visual score had significant good correlation with pulmonary function test results. However, when FEV₁ was 50% of the predicted value or greater (Table 3), mean lung density and lower attenuation volume measured from inspiratory MDCT scans correlated better with FEV₁ and FEV₁/FVC than did those values on expiratory scans. Fifth percentile at full inspiration and at full expiration and 15th percentile at full inspiration and at full expiration had a strong correlation with FEV₁/FVC and diffusing capacity of the lung for carbon monoxide (Dlco) as percentage of predicted value but a much weaker correlation with FEV₁. E/I correlated well with residual volume (RV)/TLC alone. Visual score correlated well with FEV₁, FEV₁/FVC, and Dlco. In patients with FEV₁ less than 50% of predicted value (Table 4), mean lung density and lower attenuation volume measured from expiratory MDCT scans correlated better with FEV₁ and RV/TLC than did those values from inspiratory scans. Fifth and 15th percentiles at both full inspiration and full expiration correlated well with FEV₁/FVC, RV/TLC, and Dlco, but the correlation with FEV₁ was much weaker. E/I correlated well with FEV₁ and RV/TLC. Visual score correlated well with Dlco alone.

Figures 2A, 2B, 3A, 3B, 4, 5A, 5B, and 6 show a variety of CT parameters in relation to GOLD stage of COPD. There were trends for lower attenuation volume, visual score, and E/I to increase with advancing disease stage. Trends were also observed for mean lung density and percentile of the frequency distribution curve to decrease with advancing disease stage. Statistically significant differences in none of CT parameters were found between patients with GOLD stage 0 and those with GOLD stage 1 disease. Statistically significant differences in inspiratory mean lung density were found from GOLD stage 1 (combined stages 0 and 1) to GOLD stage 4 (Fig. 2A). No significant differences in lower attenuation volume measured from inspiratory scans (Fig. 3A) or visual score (Fig. 4) were found between patients with GOLD stage 3 and those with GOLD stage 4 disease. Significant differences in expiratory mean lung density (Fig. 2B) and lower attenuation volume measured from expiratory scans (Fig. 3B) were found between patients with GOLD stage 3 and those with GOLD stage 4 disease, but no significant differences in these values were found between patients with GOLD stages 0 and 1 and those with GOLD stage 2 disease. Significant differences in fifth percentile at full inspiration (Fig. 5A), fifth percentile at full expiration (Fig. 5B), 15th percentile at full inspiration, 15th percentile at full expiration, and E/I (Fig. 6) were found only between patients with GOLD stage 2 and those with GOLD stage 3 disease.

Stepwise multiple regression analysis revealed that the combination of visual score and mean lung density at full expiration was associated with FEV₁ as percentage of predicted value (r = 0.752, p < 0.001). The following equation was derived: FEV₁ as percentage of predicted value = 316.275 - (0.980 × visual score) + (0.291 × mean lung density at full expiration).

The chronic airflow limitation characteristic of COPD is caused by a mixture of small airways disease (obstructive bronchiolitis) and parenchymal destruction (emphysema), the relative contributions of which vary from person to person [5]. Gelb et al. [11] found a strong negative correlation between diffusing capacity as percentage of predicted value and diffusing capacity per alveolar volume and CT emphysema score only in patients with an FEV₁ of 1 L or more. Among patients with an FEV₁ less than 1 L, however, the correlation was much weaker. In only 10 of 35 patients with an FEV₁ less than 50% of predicted was the CT emphysema score greater than 40, indicating marked emphysema. Those authors concluded that CT visual emphysema score was not predominantly responsible for airflow limitation in COPD and that emphysema did not appear to be primarily responsible for severe expiratory airflow limitation in most patients with severe COPD. Zaporozhan et al. [12] also reported that no differences in inspiratory to expiratory emphysema index or changes in emphysema index and lung volume were found between patients with GOLD 3 and those with GOLD 4 disease.

It remains unsettled whether inspiratory CT or expiratory CT is better for evaluating the severity of COPD. Studies [12-14] showed that the highest correlations between CT findings and physiologic variables consistent with emphysema were observed with CT measurements obtained at full expiration. Visual score correlates closely with morphologic emphysema and has better correlation with Dlco as a percentage of predicted value. It does not reflect the site of small airways disease. Expiratory quantitative CT parameters are affected by peripheral airway obstruction and air trapping. In our study, mean lung density and lower attenuation volume measured from inspiratory MDCT scans better correlated with FEV₁ as a percentage of predicted value and FEV₁/FVC than did those values from expiratory scans when FEV₁ was 50% of predicted value or greater. In patients with FEV₁ less than 50% of predicted value, mean lung density and lower attenuation volume measured from expiratory MDCT scans better correlated with FEV₁ and RV/TLC than did the values from inspiratory scans. Fifth and 15th percentiles at both full inspiration and full expiration correlated well with FEV₁/FVC and Dlco but not well with FEV₁ whether FEV₁ was 50% of predicted value or greater or less than 50% of predicted value. The percentiles also correlated well with RV/TLC when FEV₁ was less than 50% of predicted value.

Our study had limitations. The mean effective radiation dose to the chest for volumetric MDCT was 8 mSv (range, 6-10 mSv). Low-dose CT may be a clinically acceptable and diagnostically adequate technique for CT quantification of emphysema. Comparing standard-dose (effective tube current, 100-250 mAs) and low-radiation-dose (effective tube current, 30-60 mAs) techniques in the CT quantification of emphysema, Gierada et al. [15] found that low- and standard-dose emphysema indexes correlated at all attenuation thresholds. Mean emphysema indexes were higher on the low-dose scans, but the mean difference at all thresholds was less than 3%. Stolk et al. [16] using 4-MDCT imaged 10 patients with emphysema on two occasions 2 weeks apart. Scanning parameters were 140 kV, 20 mAs, 4 × 2.5 mm collimation, and effective thickness of 2.5 mm. The repeatability of the 15th percentile and the density-mask value of -910 HU was excellent with an estimated CT dose per examination of 0.7 mSv for a chest 30 cm long.

Our study was different from other studies in materials and method. Zaporozhan et al. [12] obtained paired inspiratory and expiratory MDCT scans of 31 patients who had severe emphysema due to COPD (GOLD stages 3 and 4). They concluded that emphysema volumes measured from expiratory MDCT scans better reflect pulmonary function test abnormalities in patients with severe emphysema than do the values from inspiratory scans. Changes in relative emphysema volume were found between patients with GOLD stages 3 and 4 disease. At expiration, there was a change from the large emphysema cluster (3D volume class 4, > 120 mm³) to the intermediate cluster (class 2, 8-65 mm³; class 3, 65-120 mm³) and small cluster (class 1, 2-8 mm³). The findings by Zaporozhan et al. were consistent with our findings in patients with GOLD stages 3 and 4 disease.

Using paired inspiratory and expiratory volumetric MDCT scans of 36 patients with COPD, Matsuoka et al. [17] determined the attenuation threshold value from the detection and quantification of air trapping in COPD regardless of the degree of emphysema. In that study, a lung volume less than -950 HU was segmented as emphysema and eliminated. Changes in lung volume with attenuation values between -860 and -950 HU at inspiratory and expiratory CT significantly correlated with the results of pulmonary function tests, except for Dlco in the moderate to severe emphysema group. In the minimal or mild emphysema group, all densitometric parameters correlated with pulmonary function test results. Mergo et al. [18] found that 3D volumetric reconstructions of hypoattenuating lung correlated well with pulmonary function test results and that inspiratory and expiratory data also were correlative.

Visual score is useful in imaging of patients with less severe COPD. Measurements of lung attenuation obtained from 3D lung reconstructions at inspiration and expiration reflect different aspects of the severity of COPD. Measurements from inspiratory scans better reflect airflow limitation than do measurements from expiratory scans in mild or moderate COPD (FEV₁ ≥ 50%). Measurements from expiratory scans better reflect airflow limitation than do measurements from inspiratory scans in severe COPD (FEV₁ < 50%), apart from a predetermined percentile of the lung attenuation distribution curve. The combination of several measurements including visual score and expiratory measurements may be needed for assessing the severity of COPD.

Partially supported by a grant to the Respiratory Failure Research Group from the Ministry of Health Labour and Welfare, Japan, and National Hospital Organization Research Grant, Japan.

Address correspondence to M. Akira ([email protected]).